Page Synopsis: Stem cell therapy has advanced significantly and can address a wide range of conditions. There have been a few successful and encouraging trials as detailed below, however administration of stem cell therapy has yet to emerge from laboratory settings to clinical practice, therefore, mostly it seems stem cell therapy for TBI isn't entirely yet 'au pointe'. That said I'm very interested in signing up for a trial study. Also, barring the cost, the precursor therapy appears worthwhile

Skill Level  5

Relevance:3 Technical Level:5


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page 68

I look forward to the day the relevance changes from 3 to 5

In the meantime, stem cell therapy has shown to be beneficial for a wide assay of conditions

Highly recommend reading this book in it's entirety 'The Stem Cell Cure: Remake Your Body and Mind' by Gaurav K. Goswami MD, Kerry Johnson MBA PhD


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Clinical trials on autologous bone marrow derived stem cells therapy in chronic stroke
Drug Speeds Recovery After Traumatic Brain Injury - MedicineNet


This unblinded, non randomized case control study dealt with the safety and efficacy of intravenous autologous bone marrow derived mononuclear and culture expanded mesenchymal stem cells in stroke 17.

Adult patients were recruited with the inclusion criteria as: 3 months to 2 years after stroke,

power of hand muscles of at least 2;

Brunnstrom stage 2-5;

NIHSS of 4-15, conscious and cooperative with assessments done for strength, tone (modified Ashworth),

Fugl Meyer (FM) scale for upper limb, Edinburgh handedness inventory, modified Barthel Index (mBI) and functional MRI including DTI was performed at baseline, 8 and 24 weeks of stem cell infusion.


Patients were screened and educated about stem cells and bone marrow aspiration technique prior to stem cell infusion 23. Forty stroke patients were recruited with the above inclusion criteria. Twenty were given stem cells followed by 8 weeks of physiotherapy, serving as experimental/stem cell group and 20 patients were administered physiotherapy regime alone. 50 \-60 million cells in 250 ml of saline was infused intravenously over 2-3 hours. The baseline clinical and radiological scores between the experimental and control groups were statistically insignificant. The safety profile was normal with no mortality or cell related adverse reactions in stem cell patients. On comparison between experimental and control groups, mBI was statistically significant on follow up at 24 weeks (p = 0.05). Laterality Index (LI) of BA 4 and BA 6 was insignificant at 8 and 24 weeks follow up, as also in the FA ratio, fiber length and fiber number ratio between the two groups. An increased number of cluster activation in Brodmann areas BA 4, BA 6 was observed post stem cell infusion indicating neural plasticity. The study was conclusive for safety and feasibility of intravenous autologous stem cell infusion 24,25. Stem cells may act as “scaffolds” for neural transplantation and may aid in repair mechanism 26

Stromal/stem cell implant improves motor function in patients with history of TBI


Patients with previous traumatic brain injury experienced significant improvement in motor functioning after implantation of mesenchymal stromal/stem cells, according to interim data from the STEMTRA phase 2 trial published in *Neurology*.


“Mesenchymal stromal/stem cell MSC implantation is a promising strategy for the treatment of TBI,” Masahito Kawabori,MD, PhD, of the department of neurosurgery at Hokkaido University Hospital in Sapporo, Japan, and colleagues wrote. “Allogeneic modified bone marrow-derived MSCs  SB623 cells, SanBio, Inc. are in clinical development for chronic TBI and stroke without concomitant immunosuppressants which were determined to be unnecessary based on the prior Phase 1/2a clinical study and preclinical studies submitted to the FDA


Kawabori and colleagues conducted a 1-year, multicenter, double-blind, randomized, surgical sham-controlled trial of 61 patients  mean age, 34.4 years; men, 70.5%; median time since injury, 68.9 months who were at least 12 months past the initial TBI. Patients had Glasgow Outcome Scale-Extended scores of 3 to 6 and focal cerebral injuries that were visible on MRI that correlated with chronic motor deficits. The mean Fugl-Meyer Motor Scale  FMMS score at baseline was 52.2 in patients who received the SB623 implant and 52.3 in controls.


Researchers randomly assigned patients to receive either the SB623 implant  n = 46 or sham surgery  n = 15. The treatment group was further randomly assigned to 2.5x10^6  n = 15, 5x10^6  n = 15 or 10x10^6  n = 16. They wrote that SB623 cells “are produced by the transient transfection of MSCs with a plasmid containing the human *Notch-1* intracellular domain” and “increases cells’ ability to secrete trophic factors, chemotactic factors and deposit extracellular matrix proteins which may support damaged neural cells.” The proprietary formulation is also being developed for other indications including spinal cord injury, according to SanBio.


Significant improvement of FMMS scores from baseline at 6 months served as the study’s primary endpoint. Researchers selected FMMS score, which is “well-established as a measure of motor impairment” and often used as a measurement of chronic stroke recovery, as the primary endpoint “because of its reliability and validity in measuring changes in patients with persistent motor deficits.”


FMSS scores improved more in patients treated with SB623 compared with controls at 6 months  least square LS mean, +8.3 vs. +2.3; the LS mean difference between scores was 6  95% CI, 0.3-11.8. Patients in the 5.0x10^6 group saw the greatest FMMS score improvements at 6 months  +10.9 vs. +2.4 point improvement; *P* = .002 and had the highest percentage of patients whose FMMS scores improved by 10 or more points  53.3%.


No dose-limiting toxicities or deaths occurred. Treatment-emergent adverse events occurred in 100% of patients treated with SB623 compared with 93.3% of controls, though this difference was not statistically significant. Headache of mild or moderate severity was the most common treatment-emergent adverse event in both the SB623 pooled group  50% and the control group  26.7%.


“In this interim analysis of a first double-blind, randomized, controlled clinical trial of cell therapy for chronic motor deficits secondary to TBI, treatment with SB623 cells appeared to be safe and was associated with statistically significant improvement of the Fugl-Meyer Motor Scale at 6 months,” the researchers wrote. “The favorable safety and efficacy outcomes reported here demonstrate the need for functional imaging studies and confirmatory Phase 3 clinical trials of SB623 cells for the treatment of chronic motor deficits secondary to TBI

'Advance of Stem Cell Treatment for Traumatic Brain Injury'


Recent studies have found that exogenous stem cells can migrate to damaged brain tissue, then participate in the repair of damaged brain tissue by further differentiation to replace damaged cells, while releasing anti-inflammatory factors and growth factors, thereby significantly improving neurological function. This article will mainly review the effects, deficiencies and related mechanisms of different types of stem cells in TBI

Strategies for CNS repair following TBI


Both MSC and human umbilical cord blood cells have been reported to transdifferentiate into neural and glial cell lineages. MSC transdifferentiation into neural cells was first shown in 2000 after proliferation in vitro  Woodbury et al., 2000. This study was followed shortly by reports of MSC transdifferentiation into astrocytes and neurons in vivo  Lu et al., 2001. Reports of spontaneous migration of transplanted bone marrow cell into the brain of animals and humans have also been published. The vast majority of these cells were noted to differentiate into non-neuronal cells, but some of the cells found in hippocampus and cortex displayed markers of neuronal lineage  Mezey et al., 2000; Mezey et al., 2003. However, it has been argued that these results are due to cell fusion of marrow cells with a recipient cell in the brain  Terada et al., 2002.


Subsequent studies cast doubt on in vivo differentiation of MSC into neuronal elements. One such paper did so by demonstrating that cell labels such as bromdeoxyuridine and benzamide may transfer from graft cells to host cells after elimination by an immune mediated response  Coyne et al., 2006. In light of results showing minimal engraftment in addition to rare or even questionable transdifferentiation, neural replacement has been posited to have limited ability as a current therapeutic mechanism by some authors  Walker, 2010.


While direct neuronal cell replacement with progenitor cell therapies remains audacious, other avenues remain for improving neuronal function following TBI. Axonal sprouting and cortical rewiring has been found in animal models following stroke and TBI. Evidence from animal models of TBI and stroke demonstrate that this process may be amplified by treatment with intraparenchymal transplantation of MSC  Liu et al., 2008; Mahmood et al., 2013. MSC transplantation appears to have some limited ability to promote axonal regeneration across lesions and provide neuroprotection to neurons that have undergone axotomy in a model of spinal cord injury  Novikova et al., 2011.


These histopathologic changes following treatment appear to arise with associated changes in function. In an animal model of TBI, the degree to which corticospinal tract axonal sprouting occurs within the spinal cord has been shown to have a correlation with improvement in of motor function  Mahmood et al., 2013. The central nervous system is known to have a limited ability for both axonal sprouting from uninjured neurons and regeneration from damaged neurons when compared to the peripheral nervous system. One of the reasons for this dichotomy is the differences in local environment and presence of myelin associated inhibitors such as Nogo-A, MAG & OMgp  Geoffroy and Zheng, 2014.


In vitro MSC have been demonstrated to mitigate these effects through multiple mechanisms: stimulation of neurite growth by soluble factors and contact mediated reductions in the effect of these inhibitors  Wright et al., 2007b.  In the case of MSC transplantation with collagen scaffolds following TBI, there is evidence of decreased Nogo-A synthesis by oligodendrocytes. This same study showed a decrease Nogo-A levels with MSC transplantation alone, but not to the same degree as those transplanted with the collagen scaffold  Mahmood et al., 2014. An increase in axonal sprouting with anti Nogo-A antibodies has also been shown in a stroke model. Furthermore, this increase in axonal sprouting from the contralateral corticospinal tract occurs in concert with reorganization of the undamaged motor cortex  Lindau et al., 2013.


The use of scaffolds with cell therapies, which has shown improvement in cell engraftment, may also aid in functional neurorestoration by way of axonal sprouting in major white matter tracts such as the corpus callosum and corticospinal tracts  Mahmood et al., 2013; Xiong et al., 2009. This ability to produce signs of therapeutic effect diffusely throughout the CNS is promising and may be necessary for functional recovery in severe TBI due to the high incidence of DAI. Further experimentation is necessary thought to determine if these locoregional effects are scalable to larger primates. In vitro analysis of the effect of MSC derived factors on NSC have been able to show evidence of increased neurite outgrowth even independent of glial interaction, which could be beneficial for repair of neuronal circuitry  Croft and Przyborski, 2009.


Increased axonal sprouting has also been reported following intravenous administration of MSC in rodents following middle cerebral artery occlusion  Liu et al., 2010. However, no current study appears to have investigated whether or not systemically administered progenitor cell therapy is able to mediate the axonal sprouting or regeneration in TBI.  Alternatively, replacement/repair at the site of injured brain parenchyma may be possible without the need of cell transplantation. Modulation of the constitutive cell populations at the site of injury is currently being investigated for treatment of central nervous system injuries.


Neuronal replacement may be achievable by cellular reprogramming of glial or neural progenitor cells in the brain. One pathway that has been targeted with gene transfer via viral transfection is the Notch-Hes1 signaling pathway. Stereo tactical infusion of Hes1 short interfering RNA prior to lateral fluid percussion injury has been shown to result increased differentiation of hippocampal neural progenitor cells into NeuN+ neurons and is associated with improvements in spatial memory following injury  Zhang et al., 2014. Downregulation of Hes1 is also known to result in an inverse relationship to neurogenesis and cell proliferation  Baek et


Furthermore, this downregulation may be a natural response to injury as it has been observed to occur spontaneously following TBI in rodent models to a limited degree  Yang et al., 2009. Areas without a ready supply of neural progenitor cells may benefit from reprogramming of local glial cells. Conversion of astrocytes in the striatum and cortex has been reported in vivo. This has been achieved by viral transfection with the transcription factor SOX2 in uninjured animals resulting in doublecortin + neuroblasts, but few mature neurons as shown by staining for NeuN.


Replication of this effect with SOX2 transfection is also observable in vivo following a stab wound model of TBI. In this model, no differentiation of astrocytes was noted on the non lesioned hemisphere. However, the authors in this study reported the development of action potentials and synapse formation  Heinrich et al., 2014.  A similar process has also been seen with animal models of spinal cord injury. Transfection of astrocytes with SOX2 containing lentiviruses following spinal cord hemisection resulted in induction to form neuroblasts as shown by staining for doublecortin. This transformation was observable at 4 weeks following injury and mature neurons appeared later around 8 weeks following injury.


Additionally, this method of neural replacement also resulted in synaptic formation with preexisting motor neurons  Su et al., 2014. Further increases in cell survival and maturation toward neuronal lineages has been achieved following SOX2 transfection with the use of histone deacteylase inhibitors or transfection to express noggin/BDNF  or Asc11  Heinrich et al., 2014; Niu et al., 2013; Su et al., 2014 with intra-arterial but not with intravenous administration  Kamiya et al., 2008.


Alternatively, other studies comparing intra-arterial with intravenous administration of BM-MNC have shown no difference in behavioral/functional or structural outcomes in several animal models  Vasconcelos-dos-Santos et al., 2012; Yang et al., 2013. In addition, intravenous administration was found to cause potentially beneficial attenuation of cytokines with greater decreases in IL-1β and increases in IL-10 when compared to intra-arterial administration  Yang et al., 2013.  No current studies report differences in behavioral, motor or structural outcomes with intravenous versus intra-arterial administration of stem cells in animal TBI models. Ultimately, the need for intra-arterial administration will likely depend on the degree to which functional outcomes are dependent on loco-regional versus systemic therapeutic mechanisms.


Supporting this idea is data from intravenous administration of the secretome produced by MSC on culture media. This secretome has been found to result in decreased perilesional neuronal apoptosis as well as lesion volume and possibly increase neurogenesis as shown by increased numbers of BrdU/NeuN/DAPI staining neurons at the lesion site  Chang et al., 2013. This provides some evidence that engraftment and differentiation may not be necessary to achieve neuroprotection or repair with progenitor cell therapies.  Pathways that have been implicated in the protective effects of treatment with progenitor cells and MSC in particular include paracrine mediated activation of the MAPK/Erk 1, 2 and PI3-K/Akt. In vitro analysis has demonstrated that secretory factors from MSC are able to illicit enhanced phosphorylation of MAPK/Erk 1, 2 in neurons and leads to decreased neuronal apoptosis.


This decrease in apoptosis is prevented with the addition of inhibitors of MEK1 thus preventing MAPK/Erk 1, 2 activation and inhibition of PI3-K  Isele et al., 2007. These two pathways have also been shown to be protective toward astrocytes  Gao et al., 2005. Activation of the PI3-K/Akt pathway following treatment with MSC also appears to result in increased axonal outgrowth. The activation of this pathway using cells in a transwell co-culture provides further evidence that this outcome is secondary to yet undiscovered secretory factories or paracrine effects  Liu et al., 2013.


Clinical Investigation

In review of the available literature, there is one published case series where direct autologous MSC transplantation was performed in humans following TBI. In this report, 7 patients  ages 6-55 underwent bone marrow harvest with subsequent isolation and expansion of their MSC population. The cells were then administered locally and later intravenously. No serious adverse effects were reported during a 6 month follow up period  Zhang et al., 2008. Intrathecal administration of MSC has also been performed in humans. In a series of 97 patients Tian and associates were able to demonstrate that they could safely harvest and administer autologous MSC using as much as 5 mL  1 x 106cells/mL via lumbar puncture in patients with persistent vegetative state or other deficits 1 month after injury.


In this series of patients, the greatest improvements were seen in younger patients who underwent treatment closer to the time of injury  Tian et al., 2013. The use of allogenic, umbilical cord MSC was evaluated in patients with chronic deficits following TBI. Twenty of the forty enrolled patients underwent 4 injections of 1 x 107cells  2 mL over a period of 5-7 days. As a result of the intervention, 20% of the displayed symptoms of low intracranial pressure but no other events were reported. The investigators reported statistically significant improvements in functional assessments 6 months out from treatment which was not seen in controls  Wang et al., 2013b

Neurorestorative Treatments for Traumatic Brain Injury


Although human embryonic stem cells hESCs or fetal tissues are suitable sources for cell-based therapies, their clinical application is limited by both ethical considerations and other practical challenges including tumorigenicity, cell viability and antigenic compatibility. Reprogramming differentiated cells generates induced pluripotent stem cells  iPSCs that resemble embryonic stem cells (Yamanaka, 2007


These iPSCs avoid the ethical issues and remove the major roadblock of immune rejection associated with the clinical use of hESCs, as well as potentially generate patient-specific cells for cell-replacement therapy. However, the safety and therapeutic applications of iPSCs and iPSC-derived cells must be rigorously tested in appropriate animal models before advancing to any clinical trial. The most important issue with iPSCs is potential tumorigenicity. Even with improvements in the virus-free and transgene-free reprogramming technologies, the cancer-causing possibility of the derived “safe” iPSCs/derivatives still needs to be evaluated in animal models before their clinical application for regenerative treatment.


Bone marrow stromal cells MSCs are a mixed cell population, including stem and progenitor cells, and are a promising source of cell-based therapy for TBI, since they can be easily isolated from many tissues and expanded in culture from patients without ethical and immune rejection problems (Chopp and Li, 2002


When grafted into the lateral ventricles of neonatal mouse brains, mouse MSCs migrated and differentiated into olfactory bulb granule cells and periventricular astrocytes (Deng et al., 2006 Systematically infused rat MSCs migrated into injured rat brains and survived (Lu et al., 2001 Some of the implanted MSCs expressed cell markers for neurons and astrocytes. Expression of the chemokine stromal-cell-derived factor-1 was significantly increased in the lesion boundary zone after brain injury induced by ischemia (Shen et al., 2007


The stromal-cell-derived factor-1 receptor, CXC-chemokine receptor-4, was expressed in MSCs both in vitro and in vivo (Shen et al., 2007 The interaction of stromal-cell-derived factor-1 with CXC-chemokine receptor-4 may contribute to the trafficking of transplanted MSCs into the injured brain (Itoh et al., 2009; Shen et al., 2007 Direct implantation 6 h post injury of MSCs enhances neuroprotection via activation of resident NSC nuclear factor κB activity leading to an increase in interleukin-6 production and decrease in apoptosis (Walker et al., 2010


The delayed administration 24 h or 1 week following injury of MSCs also significantly improved functional outcome in rodents following TBI (Chopp and Li, 2002; Chopp et al., 2009; Lu et al., 2001; Mahmood et al., 2004b; Mahmood et al., 2005; Mahmood et al., 2006


MSCs secrete various growth factors, including brain-derived neurotrophic factor BDNF, vascular endothelial growth factor VEGF and bFGF basic fibroblast growth factor, and increase the levels of these factors in the brain (Chopp and Li, 2002; Mahmood et al., 2004a


MSCs also induce intrinsic parenchymal cells to produce these growth factors (Mahmood et al., 2004a


After MSC transplantation, these neurotrophic/growth factors enhance angiogenesis and vascular stabilization in the lesion boundary zone where the majority of MSCs that survive in the brain are located (Mahmood et al., 2006


These growth factors also promote neurogenesis in vitro and in vivo (Jin et al., 2002; Lee et al., 2002; Yoshimura et al., 2003 In rodent TBI models, MSCs not only increased vascular density in the lesion boundary zone and hippocampus (Qu et al., 2008, but also enhanced neurogenesis in the SGZ and SVZ (Mahmood et al., 2004b


Delayed 4 days after TBI treatment with MSCs alone did not reduce lesion volume, whereas MSCs seeded in collagen scaffolds significantly reduced lesion volume, enhanced the migration of MSCs into the lesion boundary zone, and significantly improved spatial learning and sensorimotor function (Lu et al., 2007a


Even more delayed 7 days post injury transplantation of MSCs or MSCs seeded in scaffolds improved spatial learning and sensorimotor function, enhanced angiogenesis in the injured cortex and the ipsilateral hippocampus and increased transcallosal neural fibers in the injured cortex (Xiong et al., 2009


The significant therapeutic benefits of MSCs are not attributed to the few MSCs that differentiate into neural cells (Lu et al., 2001


However, MSCs appear to act as neurotrophic/growth factor generators and inducers to promote brain functional recovery via angiogenesis, neurogenesis, synaptogenesis and axonal remodeling (Chopp and Li, 2002; Chopp and Li, 2006 MSCs  or neural stem/precursor cells-seeded scaffolds may be a new and effective strategy for treatment of TBI.

The safety and feasibility of treatment with autologous MSCs were assessed in seven patients with TBI Zhang et al., 2008


In this trial, no toxicity related to the cell therapy was observed within the 6-month follow-up period. A safety study of autologous stem cell treatment in children with TBI has also been completed (, Identifier: NCT00254722; however, no data are available. This study should determine if bone marrow harvest and re-infusion is safe in children after severe TBI

Traumatic Brain Injury and Stem Cells: An Overview of Clinical Trials, the Current Treatments and Future Therapeutic Approaches


Currently, interventions to improve the lives of people with TBI in use including drug treatments, surgeries, and rehabilitation therapy—provide poor outcomes ( The use of SCs in the treatment of TBI has recently entered the clinic as a possible therapeutic application (, SCs therapy is used in regenerative medicine to restore damaged neurons. SCs are cells that showed the multipotent capacity to differentiate toward different cell types and possess the capacity to renew themselves ( In different preclinical studies, conducted on TBI animal models, stem cell transplantation has promoted the improvement of several neurological parameters ( Specifically, NSCs and MSCs—such as BM-MSCs, AD-MSCs, and UC-MSCs—appear capable of regenerating damaged nerve tissue, as demonstrated in several in vivo studies, using animal models of TBI.


NSCs derived from the lateral ventricle, the dentate gyrus of the hippocampus ( Moreover, NSCs are a type of cell capable of self-renewal, they can differentiate into neurons, oligodendrocytes, and astrocytes. Additionally, NSCs are able to release cytokines and neurotrophic factors such as brain-derived neurotrophic factor  BDNF, glial cell-derived neurotrophic factor  GDNF, and insulin growth-factors-1  IGF-1. Several studies suggest that transplanted NSCs can potentially repair and integrate neurons and glial cells at the injury site, due to their ability to release crucial molecules to maintain structural and functional plasticity ( NSCs, when administered in an experimental model of TBI, may be an effective, long-term treatment for neurological recovery after brain injury (


The MSCs are multipotent stromal cells that can be easily harvested from a variety of tissue sources such as bone marrow, umbilical cord, adipose tissue, placenta, and oral cavity ( Also, MSCs are potentially capable of differentiating into a variety of cell types including osteogenic, adipogenic, chondrogenic, and neural lineages ( Moreover, MSCs according to the definition of MSCs of must be positive for CD73, CD90, and CD105 surface markers. On the contrary, MSCs must be negative for CD45, CD34, CD14, CD11b, CD79a, and CD19 and for the major histocompatibility complex class II surface molecules (


MSCs promote the regeneration of damaged tissues through reducing inflammation response, recruiting local progenitor cells to replace lost cells and releasing trophic factors including BDNF, GDNF, vascular endothelial growth factors  VEGF, and nerve growth factor NGF ( Therefore, thanks to their proprieties, MSCs therapy can potentially be useful to repair damage following TBI ( Indeed, it was demonstrated that MSCs are able to electively migrate to the lesioned nervous tissue of the TBI rat and following differentiate towards neurons and astrocytes, in order to repair the damaged area, with consequent enhancement the motor activity after TBI (


The BM-MSCs derive from the bone marrow and showed the ability to differentiate into several cell lineage including neurons and glial cells ( It was demonstrated that BM-MSCs transplantation promotes neuroplasticity and neuronal regeneration through several mechanisms ( BM-MSCs showed anti-inflammatory effects by promoting the differentiation of lymphocytes. Additionally, BM-MSCs are able to release growth factors such as VEGF, BDNF, GDNF, NGF, epidermal growth factor  EGF, fibroblast growth factor  FGF, and neurotrophin-3  NT-3, in this way leading on the repair of the lesioned area ( Several preclinical studies showed that BM-MSCs release trophic factors into the damaged sites, that inhibit apoptosis, promote angiogenesis and stimulate host progenitor cells to differentiate toward neurons and astrocytes. In this way, BM-MSCs showed the ability to repair the lesioned tissue and recovered function in animal models of TBI (,


The UC-MSCs are obtained easily by treating the umbilical cord or the cord blood. The UM-MSCs compared to other stem cells showed several advantages such as a low immunogenicity power, less risk of rejection after transplantation, easy harvesting, and no ethical controversy ( These cells secreted neutrophil activator, NT-3, BDNF, VEGF, and FGF in order to induce neuronal regeneration and neuronal vascularization in the damaged area. It was demonstrated that UM-MSCs confer trophic support in the injured, induce the microglia/macrophage to remodel of the brain, leading to significant improvement of neurological functions (


The AD-MSCs are easily isolated from adipose tissue ( These cells have the ability to differentiate into cell types including neurons, endothelial-derived cells, and Schwann cells ( Additionally, AD-MSCs exhibit immunomodulatory properties thanks to the release of several cytokines including IL-10 and transforming growth factor-beta TGF-β ( Likewise, thanks also to the release of neurotrophic factors such as BDNF and GDNF, they showed neuroprotective properties ( It was demonstrated the AD-MSCs transplantation improvement motor activity in an animal model of TBI, suggesting that these cells might be considered for patients with TBI (


To date, studies report that the principally used stem cell routes of administration are the intravenous route and local administration by stereotactic injections ( The intravenous route has the advantage of being a non-invasive strategy, but it shows the limit that the percentage of infused cells that reaches the lesion site is very small. In addition, intravenous administration of stem cells implicates that these cells are retained by the pulmonary capillaries, thus compromising their therapeutic potential ( Hence, this route of administration results not very effective due to the large dispersion of cells between the different organs of the body, which requires the administration of a large number of stem cells. Compared to intravenous administration, local infusion of stem cells by stereotaxic injections is invasive but allows to inject stem cells directly into the injury site ( Therefore, this route of administration shows the advantage of reducing the number of stem cells used. However, the best route of administration has not yet been established, as each route shows its advantages and disadvantages


TBI is a very complex disease. Nowadays, there are no effective treatments able to reduce the effects of the primary injury, but only therapies capable of blocking their progression. In recent decades, NSCs and MSCs  BM-MSCs, AT-MSCs and UC-MSCs, have demonstrated to be a useful tool that can reduce the effects of post-traumatic brain injury. In several of the clinical studies described, BM-MSCs administrated via intravenous and via lumbar puncture, shown improvement in damaged brain areas. The same results were obtained using the UC-MSCs transplantation; however, the number of studies is fewer. Therefore, the available results encourage the use of both SCs and therapies described as useful for the treatment of TBI


Adult CNS neurons are able to grow extensively after injury if offered a permissive peripheral nerve transplant  Richardson *et al.*, 1980; David and Aguayo, 1981; Aguayo *et al.*, 1991; Xie and Zheng, 2008 These experiments not only helped to overcome the dogma that injured adult CNS axons have lost their axonal growth capability but also induced a shift in focus towards the micro-environment of injured axons, giving rise to the question, ‘What makes the CNS micro-environment so hostile for regrowth of injured fibers?’ One of the first to answer this question was Martin Berry who postulated that breakdown products of the CNS myelin are responsible for the failure of injured CNS fibres to regrow. Martin Schwab and colleagues soon discovered the differences between CNS myelin and that of the peripheral nervous system where regeneration of injured nerve fibres is known to occur  Berry, 1982; Schwab and Thoenen, 1985; Schwab and Bartholdi, 1996; Xie and Zheng, 2008


The inhibitory activity of CNS myelin was overcome in a seminal rat spinal cord injury experiment conducted by Schnell and Schwab. They showed that intraventricular injection of hybridoma cells, producing a monoclonal antibody directed against inhibitory proteins of the CNS myelin, later called NOGO A, enhanced regenerative growth of injured corticospinal tract fibres across the spinal lesion site and improved functional recovery  Schnell and Schwab, 1990


Since these pioneering studies, we have learned that, besides CNS myelin, glial scar tissue forming at the lesion site in the spinal cord or brain also impedes fibre growth. Some of its molecular constituents will be discussed later in more detail  Silver and Miller, 2004; Mueller *et al.*, 2005 Based on experiments with antagonists of myelin-associated inhibitors or glial scar-associated inhibitors or pharmacological modifiers of the neuronal growth response, performed primarily in animals with spinal injury, several mechanisms have been described to account for drug-induced axon growth or rearrangement-induced functional improvement. A recent classification distinguishes regeneration from sprouting and plasticity based on the inciting event, the timing of axonal growth and rearrangement and distance of axonal regrowth  Cafferty *et al.*, 2008


The term regeneration is used to describe the growth of injured or damaged axons over longer distances and over longer periods of time, whereas sprouting refers to growth from injured or damaged fibres or from intact fibres over moderate distances. Plasticity, in a narrow sense, describes changes in the underlying network induced by damaged fibres and correlated functional loss  Cafferty *et al.*, 2008 The most time-consuming of these is the process of regeneration which takes weeks to months to bring about functional improvements, whereas sprouting and plasticity occur at a faster rate, that is, within days or even hours of the damaging event  Cafferty *et al.*, 2008


Most of these different mechanisms have been identified in animals with spinal cord injury and another important insight gained from these experiments was that, despite their often meandering course within the spinal cord tissue, regrowing fibres are able to synapse with their proper target neurons. Just how they are guided to their synaptic partners is not actually known but re-expression of many classes of developmentally active attractive and repulsive axon guidance molecules at the site of lesion or damage might be an explanation for the proper pathfinding and paucity of aberrant connections formed. This constitutes a very encouraging sign for the development of axonal growth therapeutics and several neuroregenerative drug candidates are currently being evaluated in clinical trials with spinal cord injury patients  Baptiste and Fehlings, 2008; Gonzenbach and Schwab, 2008 Table 1 provides a summary of potential axonal growth therapeutics including their proposed mode of action and investigational status in spinal cord injury. If successful, it is envisioned that these regenerative drug approaches will be extended to other CNS injuries such as traumatic brain injury  TBI


Regenerative strategies under evaluation for spinal cord injury treatment  Therapeutic agent, Proposed mechanism of action, trial Status as of 2009


Rho inhibitor  Cethrin®

Blockade of growth inhibitory pathway| phase I/IIa


Anti-Nogo A antibodies

Neutralization of growth inhibitory myelin protein phase I/IIa


Chondroitinase ABC

Degradation of glycosaminoglycan chains of growth inhibitory proteoglycans|preclinical


Anti-NgR antibodies or antagonists

Blockade of growth inhibition mediating receptor|preclinical


LINGO-1 antagonist

Blockade of growth inhibition mediating receptor complex|preclinical


Anti-RGM A antibodies

Neutralization of growth inhibitory protein|preclinical


Rho kinase  ROCK inhibitors  Fasudil

Blockade of growth inhibitory pathway|preclinical


Sema3A inhibitor  SM-216289

Neutralization of growth inhibitory protein|preclinical


Neurotrophins  BDNF, CNTF, GDNF

Growth promotion by neurotrophin receptor stimulation|preclinical


PDE4 inhibitor  Rolipram®|Growth promotion by increasing cAMP levels|preclinical


Anti-RYK antibodies|Neutralization of growth inhibitory proteins|preclinical


Noggin  BMP-antagonist|Neutralization of inhibitory proteins|preclinical


EGFR inhibitor  PD168393|Blockade of growth inhibitory pathway|preclinical


GSK-3β inhibitor  Lithium, SB415286|Blockade of growth inhibitory pathway|preclinical


PKC inhibitor  Gö6976|Blockade of growth inhibitory pathway|preclinical


L1 cell adhesion molecule|Neurite growth promotion|preclinical


Iron-chelator  Cordaneurin®|Inhibition of collagen scar formation

Help rewrite changes to DNA?


What we certainly dont have at the moment is targeted stem cell therapy, so the devil is in the details I reckon. Just sating "stem cell" therapy is far too broad a spectrum..


can reactivate ebv hhv   I think I read somewhere there is a risk of herpes reactivation from stem cells transplant Correct me if I am wrong, I am not an expert and she did get reactivated shingles after and then went down with ME months later.


on positive testimony


"Mesenchymal stem cells  MSCs are now known to display not only stem cell multipotency, but also robust antiinflammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn's disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Current data suggests that MSCs may not only replace diseased tissues, but also exert several trophic, regenerative and antiinflammatory effects.


Cells home to areas of inflamation when reintroduced systemically either intravenously or otherwise, typically most will go to the lungs, but many also go to the gut, and some to the brain, this has been proved in research. Also once extracted from fat they are separated, primed, chemically potentiated, only then reintroduced to the system. Mesemchycal stem cells extracted from fat have been shown to repair thyroid, diabetes, help with conditions like chrons.


Also my own testimony is my lymphocytes have returned to normal range for the first time in 7 years just months following a stem cell procedure, they were well below reference range every single time before this without fail. Im pretty sure this is not a placebo effect. I am noticing little shifts, but it is a process."

Stem cell application in neurorehabilitation' Oxford Textbook of Neurorehabilitation (2 ed.)


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Advance of Stem Cell Treatment for Traumatic Brain Injury











                  Gulf Coast Stem Cell Therapy Center and CFS click to openThis is where regenerative medicine, and in particular stem cell therapy, may provide hope. CFS and the Stem Cell RevolutionWhereas most cells divide into copies of themselves during cell replication, stem cells are particularly fascinating in that they can evolve into different types of cell depending on their type. Stem cells can be very broadly separated into embryonic stem cells  ESCs, found only within the cell mass of the blastocyst and somatic stem cells, found in various locations within the body including the bone marrow, adipose  fat tissue, skin, brain, eye and lung. Umbilical cord cells are a special category of the embryonic variety of cells. Whereas ESCs are valued because of their totipotency  inherent ability to divide into any cell found in the adult body, somatic stem cells, though slightly more limited, are free of the ethical complications surrounding the use embryonic cells. In particular, autologous stem cell treatments – those which utilize the stem cells of the patient’s own body – are completely innocuous from a moral standpoint. Stem cell treatments for CFS  and other systemic conditions use autologous mesenchymal stem cells  MSCs, taken either from bone marrow  bone marrow derived stem cells, BMDSCs or from adipose tissue  Adipose-Derived Stem Cells, ADSC. The latter are becoming more popular since they are the most plentiful and can be more easily harvested than those in bone marrow. Further, the chances of better outcomes increase with the increasing quantity of cells, which makes adipose stem cells the preferred source for treatments, as offered by the Mississippi Stem Cell Treatment Center. Liposuction is also a more comfortable procedure than the extraction of bone marrow from the hip bones. Whereas many of the headline-grabbing stories regarding stem cell successes focus on results from treatments delivered as part of highly specialized clinical trials, these are neither available nor suitable for CFS sufferers. However, there is a growing body of evidence to back up claims that MSCs can operate at a systemic level by exerting a anti inflammatory effect, by repairing damaged tissue  this happens naturally in response to any injury and by modulating the immune, hormonal and circulatory systems. This is good news for CFS patients, since the harvesting and deployment of MSCs is currently being carried out in specialized facilities, like the Mississippi Stem Cell Treatment Center, throughout the United States. Patients interested in receiving stem cell treatment should, of course, thoroughly research the protocols and procedures involved, the facility and equipment used and the experience and competence of the team administering the treatment. Stem cell treatment for CFSHow Stem Cells are Helping CFS Sufferers ?While it is advisable to treat anecdotal evidence with caution  the Mississippi Stem Cell Treatment Center does not use anecdotes for marketing purposes, CFS sufferers who have undergone Stem cell treatment for CFS are reporting outcomes consistent with an overall systemic improvement. Recipients have reported a reduction in pain, including headaches, with some stating their pain has been eliminated completely. Other patients have reportedly experienced reduced swelling, improved co-ordination and higher energy levels and some have noted an improvement in their sleeping patterns. As research continues, both into the potential causes of CFS and into the efficacy of stem cell treatments for a steadily increasing range of pathologies, there is good reason for frustrated sufferers to be optimistic that a remedy may one day be found for this most enigmatic of syndromes. Do you suffer from chronic fatigue syndrome? Are you frustrated with your current treatment plan? To find out more about the Mississippi Stem Cell Research Center, our luxurious and state-of-the-art facilities and our pioneering autologous stem cell treatments, please visit our website at or contact us on  886 885 4823 

                  Stem Cell Clinics in California Autologous Stem Cell Therapy Institute Over the decades, multiple procedures have been developed to achieve a more youthful and vibrant look such as using fillers to smooth out the deep wrinkles and lines on the face. Most of these consist of temporary fillers that eventually are absorbed and wear off. With the advance of Stem Cell technology, we can now use your own stem cells as fillers. This procedure is called Autologous Stem Cell treatment – a long term rejuvenation that doesn’t involve any foreign substance that is not your own. By harvesting stem cells from your adipose tissue and peripheral blood, the procedure restores youthful contour on the back of your hands. Autologous Stem Cell Therapy Institute was founded in 2010 by Dr. Edmund Chein, MD.. Dr. Chein received his orthopedic and rehabilitation medicine training from the Los Angeles County- University of Southern California Medical Center. Dr. Chein was the first in the United States to use Human Growth Hormone for anti-aging in adults. In 1994 he founded the Palm Springs Life Extension Institute. Every year, hundreds of new patients come to the Institute from all over the world to get bio-identical hormone supplementation to slow down the aging and reverse biological age by lengthening the telomeres in their DNA. In 2012, Dr. Chein added Autologous Stem Cell Therapy to cure some of the disabling orthopedic conditions which Growth Hormone cannot cure, and enhance the youthful look of the hands of his patients. What other conditions can Autologous Stem Cell Therapy treat?Orthopedic conditions such as:Osteoarthritis – IRB approved protocolTendinitis, partially torn tendons, ligaments, and meniscus of the knees. – IRB approved protocol IRB = Institutional Review Board – a FDA-approved research project The Importance of Growth Factors in the Success of Your Stem Cell TherapyThere are many types of stem cells used in stem cell therapy today. The most common and safest is autologous stem cell therapy, which uses one’s own stem cells collected from one’s own adipose tissues and peripheral blood. When your own stem cells are used as fillers, the stem cells become your skin cells, making the cosmetic correction permanent and natural. It is well known that the age of the donor  you, in the case of autologous stem cell therapy and the donor’s level of growth factors, such as IGF-1, growth hormone, testosterone, and estrogen, are directly proportional to the number and quality of the donor’s stem cells. In order to have a good quantity and quality of stem cells collected, we check the levels of the above-mentioned growth factors in the donor before starting the therapy. We recommend bringing growth factors up to their optimal levels in case the levels of growth factors in you are deficient due to age or health status, in order to maximize the rate of success of your stem cell therapy. Adipose Cell ExtractionWe have recently acquired the Belgium-made Nutational Infrasonic Adipose Tissue Liposuction machine to obtain adipose tissue-based stem cells for transplant. It is the most advanced instrument for obtaining good quantity and quality of autologous stem cells from one’s adipose tissues to transplant to and regenerate the hands, as well as tendons, cartilage and ligaments in joints. This also allows us to combine adipose tissue-derived stem cells with those derived from peripheral blood with abundant growth factors. Business Website Address: http://www.autologous-stem-cell-therapy-institute.comBusiness Phone Number:  760 322-0011Business Address: 2825 E Tahquitz Canyon Way, Palm Springs, CAZIP Code: 92262Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA What can stem cells do?Stem cells have the potential to:
• Replace cell tissue that has been damaged or destroyed by illness,
• Replicate themselves over and over for a very long time,
• Help scientists understand the origin of human biological development
• Help scientists understand healthy & diseased cells in hope of creating treatments & cures for many diseases.
 The National Institutes for Health  NIH notes that stem cells “have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells for as long as the person or animal is still alive. When a stem cell divides, each ‘daughter’ cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. A more detailed primer on stem cells can be found at” What is a stem cell?They are in a sense, the cells from which all else “stems”. Bioethicist Alexander Capron of the World Health Organization described a stem cell as, “the foundation of organisms, the stalk from which everything buds and branches.” Stem cells may be either embryonic or adult  somatic. As a fertilized egg divides, the multiplying embryonic stem cells differentiate into or become all of the diverse tissues of the body, such as lungs, liver, brain, hair, heart. What role do stem cells play in human biology?Stem cells regenerate lost or damaged cells. For example, when a person gives or loses blood, stem cells will replenish the supply. If the skin is damaged, it generates new skin cells as it heals. Since stem cells have the ability to generate new tissue specific cells, this area of medicine is often called “regenerative medicine”. All animals, including humans, start from one cell, which results from fertilization of an egg by a sperm. The resulting one cell contains all of the animal’s genetic material or DNA and is capable of developing into a complete organism. As the cell divides, the resulting cells or daughter cells, will still contain all of the DNA, while at the same time becoming specialized, and more restricted in their ability to become all types of organs and tissues. Are stem cells currently used to treat disease?Yes, adult or somatic stem cells have been used for some time to treat disease. For example, blood stem cells created in the bone-marrow are used in “bone-marrow transplant” as a common therapy for various blood based diseases such as leukemia and aplastic anemia. Organ transplantation also uses stem cell technology. What are the stages of human development?The National Bioethics Advisory Commission  NBAC provided a simple outline of human development: 1. the developing organism is a zygote during the first week after fertilization, 2. the organism is an embryo during the 2nd – 8th weeks of development 3. the organism is a fetus from the 9th week of development until the time of birth. What is an embryonic stem cell?Embryonic stem cells come from the “inner cell mass” of a group of cells called a blastocyst. The blastocyst is an early stage of development known as the “zygote” that occurs within the first 4-6 days after fertilization. Once the “inner cell mass” or embryonic stem cells are removed from the blastocyst, the cells may be kept alive in a petri dish under specific laboratory conditions. Such cells are pluri-potent meaning they may become any cell in the body. What is an adult or somatic stem cell?They are stem cells found in the tissue and organs of organisms that have the potential to become their tissue of origin. Essentially, adult or somatic stem cells are tissue specific stem cells that will have a specific occupation within the organism, for example, embryonic stem cells that differentiate or become heart stem cells will form heart tissue. Such cells have the ability to replenish or maintain tissues that have a limited life span, such as skin and intestines. For example, the human intestine sheds and replaces 100 billion cells daily by dividing stem cells that generate replacements for the short-lived cells. Thus, adult or somatic stem cells are “differentiated” or specifically assigned to the creation or replenishing of cells in specific tissues or organs. What is differentiation?Differentiation is the process in which a cell, such as a stem cell, specializes in the creation or replenishing of cells in specific tissues or organs in the body. The process occurs through the activation  “turning on” or inactivation  “turning off” of specific genes in the cells. The turning on/turning off process results in the development of cells that are assigned specific tasks such as creating the heart or replenishing the lining of the intestine. What are the sources for embryonic stem cells?1. Excess fertilized eggs from in-vitro ferilization clinics,
2. Using IVF procedures with donated oocytes and sperm to make blastocysts for research, or
3. Somatic Cell Nuclear Transfer  SCNT
 What is Assisted Reproductive Technology  ART?Assisted Reproductive Technology or ART includes all treatments or procedures that involve the laboratory handling of human eggs and sperm for the purpose of fertilizing an egg and helping a woman become pregnant. Business Website Address: https://stemcell.ucla.eduBusiness Phone Number:  310 825-4958Business Address: 615 Charles E Young Dr S, Los Angeles, CAZIP Code: 90095Golden Gate Stem Cell After 30 years of performing a wide variety of orthopedic procedures to treat sports injuries and arthritic conditions, we are excited to offer the investigational use of Adipose-Derived Stem Cells  ADSC’s for clinical research and deployment.  This technology adds to our toolbox of treatment choices for the patient with orthopedic and degenerative conditions. Our treatments are part of an investigative program begun in 2010 by 2 surgeons in Southern California. As affiliates of the Cell Surgical Network®  CSN, we utilize the network’s specific protocols for harvesting fat cells followed by deployment into injured joints or tendons.  We are committed to working with orthopedic patients looking for alternatives or additions to traditional surgical options and those who are not yet ready for total joint replacement. An online application/interest form is filled out, and then a free 10-minute informational phone call is provided if you meet our criteria for stem cell treatment. If appropriate, a consultation, preferably in the office, or via Skype if you are at a distance, is then done to review the specifics of your problem and determine if you are a candidate for adipose-derived stem cell  ADSC  treatment. Meet and GreetYou have made an important decision to have stem cell deployment. It’s exciting that these tools are now available for therapeutic use. Stem cell therapy with your own stem cells may very well be the next significant advancement in medicine.

Local Anesthesia & Harvesting FatPatients have their fat harvested in a special treatment facility under a local anesthetic. The procedure lasts approximately twenty minutes, using specially designed equipment to harvest about 50cc of fat. Preparation After harvesting the fat cells, the next step is to isolate the cells. This is accomplished by separating the fat cells and stem cells. The process used by Golden Gate Stem Cell Treatment Center yields an extremely high number of stem cells. DeploymentDepending on the type of deployment required, stem cells can be injected through veins, arteries, subcutaneously, or directly into joints. All of these are considered minimally invasive methods of introducing stem cells. In the right environment, these cells can change  differentiate into bone, cartilage, muscle, fat, collagen or neutral tissue. Because it is your own DNA material, there is no rejection. The whole process takes less than three hours. Business Website Address: http://ggstemcell.comBusiness Phone Number:  415 923-3028Business Address: 2100 Webster St, San Francisco, CAZIP Code: 94115Institute for the Biology of Stem Cells  IBSC at UC Santa Cruz About the IBSCMISSIONThe Institute for the Biology of Stem Cells  IBSC at UC Santa Cruz aims to support and advance stem cell research by promoting interdisciplinary discoveries in biology, engineering, and information science to enable cures. The Institute for the Biology of Stem Cells  IBSC encompasses research, training, and facilities. The institute was made possible by the high quality of biological and engineering research on the UCSC campus and by the California Institute for Regenerative Medicine  CIRM, which in September 2005 approved funding for UCSC to establish a training program in stem cell research. Funding from CIRM also made possible the UCSC Shared Stem Cell Facility and other major projects that have supported stem cell research on this campus, such as a major facility award that funded the IBSC space in the new Biomedical Sciences Building. Business Website Address: https://stemcell.soe.ucsc.eduBusiness Phone Number:  831 459-1399Business Address: 1156 High St, Santa Cruz, CAZIP Code: 95064International Stem Cell Corporation OVERVIEWInternational Stem Cell Corporation  ISCO is a publicly-traded clinical-stage biotechnology company with a powerful new stem cell technology called human parthenogenetic activation that promises to significantly advance the field of regenerative medicine. Parthenogenetic  from the Greek parthenos meaning “virgin” and genesis meaning “birth” activation utilizes unfertilized human eggs to create parthenogenetic stem cells  hpSC that can be immune-matched to millions of people. As a result, a relatively small number of hpSC lines could provide enough immune-matched cells to cover a large percentage of the world’s population. ISCO’s scientists are focused on using hpSC to treat severe diseases of the nervous system, joints, and liver where cell therapy has been proven clinically effective but is limited by the availability of safe immune-matched human cells. Business Website Address: http://www.internationalstemcell.comBusiness Phone Number:  760 940-6383Business Address: 5950 Priestly Dr, Carlsbad, CAZIP Code: 92008Irvine Stem Cell Center DR. TOWHIDIANDr. Hamid A. Towhidian founded the Irvine Stem Cell Center and has specialized in the use of advanced technology.  He incorporates his advanced education and specialized knowledge by adopting innovations and medical techniques introduced around the world. He has practiced fat stem cell therapy for years in natural breast and buttocks augmentation.Irvine Stem Cell Center provides services for cosmetic and therapeutic purposes. Regenerative stem cell therapy assists the body in repairing, replacing, restoring, and regenerating infected or damaged cells, tissues, or organs. It elevates the natural healing system of the body, resulting in an improved quality of life with extended life spans. Our goal is to slow down the aging process and enhance the natural beauty of our clients. Dr. Towhidian is a graduate of George Washington University and is a former staff member of Hoag Hospital, Irvine Regional Hospital, CHOC, and St. Joseph Hospital of Orange. He has more than 30 years of experience practicing cosmetic and dermatology surgery. OUR MISSIONAt Irvine Stem Cell Center, our mission is to provide the safest and most effective methods to enhance the quality of life and natural beauty of each of our clients. We use the most cutting edge technology and advanced innovations for cosmetic procedures and therapeutic use. OUR VISIONIrvine Stem Cell Center introduces Regenerative Stem Cell Therapy to improve the quality of life of our clients by activating the body’s natural healing; enabling the body to repair, replace, restore and regenerate. Transform the way our clients look and feel, improving their health and confidence. OUR GOALOur goal at Irvine Stem Cell Center is to help slow down the aging process by utilizing the latest advances in technology, and providing our clients with an exceptional overall experience. We aspire to improve our clients’ self-esteem with a positive self-image, looking and feeling younger than they have in years. OUR VALUESCustom consultations are provided at Irvine Stem Cell Center to fully understand the unique needs of each client, ensuring our clients receive the best care and service. We offer financing options so that everyone has the opportunity to improve their lives, to look youthful and feel rejuvenated. A STEM CELL is basically any cell that can replicate and differentiate. This means the cell can not only multiply, but it can also turn into different types of tissues. There are different kinds of stem cells. Most people are familiar with or have heard the term “embryonic stem cell.” These are cells from the embryonic stage that have yet to differentiate – as such, they can change into any body part at all. These are then called “pluripotential” cells. Because they are taken from unborn or unwanted embryos, there has been considerable controversy surrounding their use. Also, while they have been used in some areas of medicine – particularly, outside the United States – they have also been associated with occasional tumor  teratoma formations. There is work being conducted by several companies to isolate a particular line of embryonic stem cells for future use. Another kind of stem cell is the “ADULT STEM CELL.” This is a stem cell that already resides in one’s body within different tissues. In recent times, much work has been done isolating bone-marrow-derived stem cells. These are also known as “mesenchymal stem cells” because they come from the mesodermal section of your body. They can differentiate into bone and cartilage, and probably all other mesodermal elements, such as fat, connective tissue, blood vessels, muscle and nerve tissue. Bone marrow stem cells can be extracted and because they are low in numbers, they are usually cultured in order to multiply their numbers for future use. As it turns out, fat is also loaded with mesenchymal stem cells. In fact, it has hundreds if not thousands of times more stem cells compared to bone marrow. Today, we actually have tools that allow us to separate the stem cells from fat. Because most people have adequate fat supplies and the numbers of stem cells are so great, there is no need to culture the cells over a period of days and they can be used right away. Business Website Address: http://www.irvinestemcellcenter.comBusiness Phone Number:  888 499-3623Business Address: 16520 Bake Pkwy #115, Irvine, CAZIP Code: 92618Irvine Stem Cell Center Clinic 2 Laguna Beach, CA DR. TOWHIDIANBusiness Website Address: http://www.irvinestemcellcenter.comBusiness Phone Number:  888 499-3623Business Address: 1833 S Coast Hwy #130, Laguna Beach, CAZIP Code: 92651Lander Regenerative Urology ELLIOT B. LANDER, MD, FACSCertified Diplomat of the American Board of UrologyFellow of the American College of SurgeonsMedical Director California Stem Cell Treatment Center, Inc. Elliot B. Lander, M.D.F.A.C.S. is a Board-Certified Urologic Surgeon who has been involved in cutting edge translational stem cell treatment since 2010. After 22 years of successfully practicing general urology, Dr. Lander has created California Regenerative urology- the first urology practice in the United States that is focused on regenerative medicine and dedicated to providing his urologic patients with access to novel regenerative therapies including growth factors and adult stem cells in addition to elite traditional urologic care. Dr. Lander is Co-Founder and Co-Medical Director of the world-renowned California Stem Cell Treatment Center where patients from all over the globe have had access to investigational regenerative therapies. Dr. Lander is also Co-Founder and Co-Medical Director of the Cell Surgical Network which is a national and international clinical research collaboration devoted to the study of adult mesenchymal stem cells for various degenerative diseases. Dr. Lander created this unique practice to join his knowledge and experience with stem cell-based therapies with his practice of urology to tackle complex problems including Erectile Dysfunction, Peyronies Disease, Interstitial Cystitis, and many others. Business Website Address: http://landerurology.comBusiness Phone Number:  760 776-0040Business Address: 72780 Country Club Dr #301, Rancho Mirage, CAZIP Code: 92270Michelson M.D. Cosmetic Surgery Why choose MICHELSON COSMETIC Surgery, Aesthetic & Anti-Aging Center? “Less is more” is the watchword at Michelson Cosmetic Surgery and Anti-Aging Center. In addition to traditional cosmetic surgery-eyelid, face and neck lift, tummy tuck and breast augmentation and lift, my practice offers the most advanced laser, plasma, shockwave technology to achieve remarkable rejuvenation and restoration of youthful countenance. Less downtime, less risk, and more natural aesthetic results characterize Southern California Cosmetic surgeon Dr. David Michelson’s approach to achieving extraordinary results in a safe, friendly, affordable context. The staff at Michelson Cosmetic Surgery are friendly, competent, bilingual and professional. Dr. Michelson’s outpatient office-based surgicenter is approved by American Association Accredited Hospitals and Clinics. We offer FaceTime, Facebook, and Skype consults. We also offer Dr. Michelson’s new skincare line, visit our new online store to learn more about MichelsonMD. Business Website Address: http://venturastemcell.comBusiness Phone Number:  805 485-3888Business Address: 1889 N. Rice Avenue, Suite 201, Oxnard, CAZIP Code: 93030Newport Beach Stem Cell Treatment Center Newport Beach Stem Cell Treatment CenterThe Newport Beach Stem Cell Treatment Center provides cutting-edge care for patients with a wide variety of degenerative disorders using adult stem cell regenerative therapy. Our highly trained physicians and medical team are focused on providing you with the most innovative techniques and advanced procedures for harvesting and deploying stem cells from your own fat. We are committed to clinical research and the advancement of regenerative medicine.  Our Doctor and StaffWe are dedicated to the principles of personalized patient care and individualized attention. Our plastic surgeon, a pioneer in liposuction, and topnotch team of registered nurses and technicians are experienced in harvesting and deploying adult stem cells. In addition, our comfortable in-office surgery center is fully accredited by the Institute for Medical Quality, a division of the California Medical Association. Our goal is to provide you with the best possible care in a friendly and professional atmosphere.  Stem Cell TechnologyFat is the body’s most abundant repository of adult stem cells, containing thousands of times more stem cells than bone marrow. New technologies at the Newport Beach Stem Cell Treatment Center make it possible for us to remove a few ounces of a patient’s fat through liposuction, separate out the stem cells in a special process that yields extremely high numbers of viable cells, and return them back into the patient’s body via IV or injection. Performed in a physician’s office under sedation and local anesthesia and using a sterile “closed system” technology  so the cells never come into contact with the environment, there is minimal discomfort and risk of infection. And because the cells come from the patient’s own body, there is no risk of rejection or disease transmission. Business Website Address: http://nbstemcell.comBusiness Phone Number: 949-721-1113Business Address: 360 San Miguel Drive, Suite 207, Newport Beach, CAZIP Code: 92660Directory of stem cell clinics in other states 



The Stem Cell Cure: Remake Your Body and Mind

stem cell therapy is proven to be effective in the treatment of many common conditions from arthritis and back pain to Alzheimer’s, Parkinson’s, and cancer. This book is an accessible and informative introduction to the amazing powers of Stem Cell Therapy – the biggest revolution in medicine since the discovery of penicillin, and a wave of the future

The Cure All


The treatment uses stem cells–undifferentiated cells that can develop into specialized tissues. In Berman’s procedure, the stem cells will come from my own fat. He claims that by circulating them through my body intravenously, they will locate sites of inflammation–whether herniated disks or torn ligaments or arthritis–and repair them. The scientific backing is shaky. There is little quantifiable evidence to defend his claim, which he freely admits. But then he points to his track record. He says he has successfully treated more than a thousand patients, and he happily gives me names and phone numbers.


One is Lamon Brewster, a former heavyweight boxing champion. In 2010, Brewster went up against the Finnish boxer Robert Helenius, a.k.a. the Nordic Nightmare. The two were pretty well matched, but Helenius had the reach. At 6’6″ he towered over 6’2″ Brewster, and in the eighth round, he landed a series of devastating hooks to Brewster’s face. Less than a minute later, the referee called the fight. A few days after that, Brewster learned that his cornea and iris were severely damaged. Within a few months, he lost all sight in his left eye.


The damage, he was told, was irreversible. Then he heard about Berman’s therapy. With nothing to lose, he gave it a shot. Months after he received stem cell injections, his vision started to return. “It’s getting better each day,” he says when I call. He also claims the benefits extend to other parts of his body: “I had boxed a long time and suffered chronic pain. But I didn’t realize I had all these issues until they started to go away after my treatment.”


“No one has proved they’re safe or effective. People are paying a lot for these treatments with no assurances.”


To someone beset with chronic back pain, the whole thing sounds too good to be true. I’ve been down the alternative-therapy road before. And I am well aware that many people view clinics like Berman’s as potentially dangerous sham operations that promise the impossible. But chronic pain can make even the most rational person irrational. As soon as I get off the phone with Berman, I book my ticket to California.



Scientists have known of stem cells since the 1950s, but the field of regenerative medicine has only really taken hold in the past 15 years or so. In that time, researchers have managed to figure out some of the basics: Stem cells appear to serve two purposes–as a foundation for all tissue in a growing embryo and as a means of repair and replacement in mature tissue. Broadly, they come in two varieties: embryonic (found only in embryos) and adult (which live throughout the body). Embryonic stem cells can differentiate into all 220 tissues in the human body. Adult stem cells typically differentiate into their tissue of origin. For example, those in bone marrow tend to grow into red blood cells, white blood cells, or platelets but not nerve cells. In 2006, researchers found a way to turn adult stem cells into embryonic ones (called induced pluripotent stem cells), but the work is new and the implications still unclear.


Berman’s procedure relies on adult stem cells. He collects a small amount of a patient’s fat, adds enzymes to digest away the scaffolding that holds the cells in place, and then uses a centrifuge to separate the components. What he collects is called a stromal vascular fraction (SVF). It’s a mix of platelets, growth factors, endothelial cells, T cells, red and white cells, and, of course, stem cells. Berman then injects that SVF back into the patient.



On a basic level, the procedure makes sense. Stem cells help repair tissues, so why not add them to damaged areas? The trouble is that beyond the basics, stem cells are far from understood. Scientists, for example, still don’t know why a given stem cell will differentiate into one tissue and not another, or what prompts cell replication to turn on or off. They also can’t predict when some stem cells will go rogue and turn into unwanted masses. Until scientists learn more, it will be impossible to say with complete confidence that any treatment comes without significant risk.


But studies are under way. In the past few years, a number of clinical trials have launched to explore cell-based therapies for strokes, spinal cord injury, and Parkin­son’s disease, among other disorders. The FDA is studying eight lines of adult stem cells for their ability to repair hearts, bones, and cartilage. It also recently cleared a cell-based multiple sclerosis drug for a Phase I clinical trial. That work is encouraging, but even so, there’s a big divide between trials like these and safe, effective therapies.


Although already in use, SVF treatment has not yet bridged that gap. Berman still doesn’t understand how exactly it works, which he openly concedes. His best guess is that it’s not one factor. The stem cells in the SVF probably help repair tissue, but so do the growth factors and T cells. “These are complex processes, and we don’t have the technology to pinpoint the exact mechanism,” he says.



That’s not to say Berman is doing anything illegal by offering a treatment he doesn’t fully comprehend. He’s not. He’s not even doing anything unethical. He is healing patients who could not be healed. “People are indeed having amazing successes,” says Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in North Carolina. But, Atala says, we need controlled studies to truly understand why. Until those happen, getting SVF is a little like gambling: You pay your money, you take your chances.



Stem Cell Dangers



A few weeks after my MRI, I arrive for my experimental procedure at Berman’s Palm Springs clinic. After I check in, Berman joins me in the waiting room. He tells me the first step is the stock-in-trade of plastic surgeons: a little liposuction.


He walks me to an examination room and asks me to lie on my stomach. He pulls up my shirt. With a needle full of anesthetic, he numbs my left love handle–no shortage of fat there, sadly. The drug is toxic to stem cells, he tells me, so he’s careful to not inject it too deeply. Berman then makes a quarter-inch incision, inserts a small tube, and begins vacuuming. It doesn’t feel like much, a light scraping, and there’s a quiet hum. Within 10 minutes it’s over. Berman places a Band-Aid on the wound and gives the fat over to a lab tech who will render it into the SVF. In about an hour, the sample will be streaming through my circulatory system.



The procedure seems effortless. Could it be so easy to get well? Many think not.


Leigh Turner, an associate professor at the University of Minnesota’s Center for Bioethics, finds the various SVF therapies dubious. “No one has proved they’re safe or effective,” he says. “People are paying a lot of money for these treatments without any assurances.”


Paul Knoepfler, a biomedical scientist at the Institute for Regenerative Cures at the University of California at Davis, put a finer point on it: “This is a for-profit human experiment,” he says. Knoepfler maintains that stem cells could potentially form bone or cartilage in unwanted areas. He points to a case in Portugal in which a woman was treated with stem cells taken from her nose and implanted in her back to help cure paralysis. Eight years later, doctors found a lump of nasal tissue in her spine. In another case, a teenager treated at a Russian clinic with fetal stem cells for a nerve disorder ended up with a brain tumor. Neither treatment was SVF–and there is no direct evidence that SVF could lead to such results–but the risks can’t be ruled out. In one recent study in goats, SVF increased spinal inflammation and spinal disk degeneration.


“This is a for-profit human experiment.”


Despite this, Berman argues that SVF is safe. “We’ve had a thousand patients and haven’t had any significant adverse reactions,” he says. He also records his cases and says he will post them online as studies at PubMed and


A few years ago, he started something called the Cell Surgical Network, a group of about 50 doctors that includes cardio­logists, radiologists, anesthesiologists, and neurosurgeons, all of whom offer SVF therapy. The more practitioners, Berman says, the more data they have.


Berman also points to the success of SVF therapy in other patients: racehorses. In the early 2000s, a company now called Vet-Stem began offering SVF to veteri­narians, who can more freely use experimental procedures. One of those early to adopt it was Ross Rich, former owner of Arizona’s Cave Creek Equine Surgical and Diagnostic Imaging Center. “I was skeptical,” he says, “but I had some horses that were very expensive and couldn’t get them healed after 18 months.” Rich mentioned the treatment to his clients, and they wanted to give it a try.



“We injected the stem cells into the injured area, and three months later they were fully recovered,” he says. “I’d never seen anything like it. These used to be career-ending injuries, and now it’s like no big deal.” Vet-Stem claims to have treated thousands of horses successfully, and Rich has published studies that describe success rates of 80 to 90 percent. Plus, horses don’t experience a placebo effect. He was so convinced of SVF’s effectiveness that last spring, he and his wife got it for their back, knee, and ankle pain. Rich says they have seen dramatic improvements.


This comes as a comfort to me as I wait for my SVF to be prepared. I like the idea that a thousand people and thousands of horses have come before me incident-free. But I still have concerns. For one, most people treated with SVF received it only within the past several years. The long-term impacts of this therapy are still unknown. Also, it’s great that it has worked so well for so long in horses, but I’m not a horse.



As I sit waiting for my fat to be centrifuged, I cannot help but perform a grim calculus. What’s worse: Living another year or 10 with chronic pain or undergoing an unproven treatment? I could still back out. I could, without explanation, walk out the door, hop in my rental car, and spend the rest of the afternoon sitting poolside at my hotel in Palm Springs. All I would lose is a little fat from my left love handle (and every bit counts). Once I get the SVF injection, there is no turning back.



About an hour after my liposuction, a nurse walks into the room with a vial of my SVF. She tells me the sample contains about 50 million cells, which is normal. Most of it will be applied through an IV drip, and then the doctor will inject some below my left shoulder blade. Am I ready? she asks. I pull up my shirtsleeve and offer my arm for the IV.


Almost as soon as the needle enters my forearm, a mix of stem and immune cells are coursing through my bloodstream.


Because it’s unclear how the therapy works, Berman uses an IV drip to circulate the cells through the body. That way, they can attack inflammation wherever they find it. This seems a bit suspicious. Without genetic reprogramming, it’s unclear if adult stem cells from one tissue can target inflammation in another. I hope that I have not made a big mistake.



I sit with the drip for a while, and after about 30 minutes, an orthopedic surgeon named Jonathan Braslow walks in and asks about my back pain. I explain that it hovers between my left shoulder blade and my spine. Braslow seems familiar with the location and thumbs his way around until he finds the spot. “That’s it,” I say. “That’s where the pain is.”


“Okay, here we go,” he says. The needle sinks in deep. The tension in his arm releases as the SVF enters my shoulder. So this is what commitment feels like, I think to myself. Minutes later, I am out the door.



Although SVF therapy may be legal now, its future is murky. In December, the FDA released draft guidance concerning stem cells derived from adipose tissue. It was bad news for Berman. Typically, the agency regulates drugs but not surgeries. What distinguishes the two, at least in the case of biologic therapies, is the concept of mini­mal manipulation. If the patient’s tissue is removed and used in such a way that it retains its characteristics, that qualifies as minimal manipulation, and the procedure classifies as a surgery. If the tissue doesn’t retain its characteristics, the FDA deems it more than minimally manipulated, and the treatment is considered a drug. That means long and expensive clinical trials.


The agency’s draft guidance clearly states that stem cells drawn from adipose tissue are more than minimally manipulated. Enzymatic digestion and separation by centrifuge leaves doctors with something very different from plain old fat. According to Turner, the bioethicist at the University of Minnesota, the FDA position is a strong signal of coming regulation. But when that will arrive is anyone’s guess. For now, SVF clinics are in the clear. “Draft guidances are not legally enforceable,” he says. “If you were to extrapolate from the past into the future, I’d say we’re going to see more of these clinics.”


When I reach Berman by email after the FDA announcement, he’s unfazed. “The entire purpose of the FDA mandate is to prevent the transmission of communicable disease,” he writes. “Since everything we use is FDA-approved, even if not approved specifically for making SVF, as surgeons, we can do whatever we want as long as there’s no risk of disease transmission.”


While things get sorted out, Berman says, the Cell Surgical Network is building a cryogenic library where patients can store stem cells, much like women store reproductive eggs. As we age, we lose stem cells. Wouldn’t it be nice to dip into a stock of frozen ones to save a limb or stave off crippling arthritis? “I think transplants will be a thing of the past,” says Rich, the veterinarian. “In the future, you might be able to call a company that has the best stem cells for the damaged body part and have them overnighted.”



A week after my SVF, I’m at home working when I realize that, for the first time in seven years, I have no back pain. I just feel normal. On various stem cell–related sites, I’ve seen plenty of warnings that improvements to a condition may not be the result of a stem cell treatment. Relief can come from some mixture of the placebo effect, concurrent therapies, and natural healing. But I hadn’t had a placebo effect from any of my other treatments, I haven’t been doing any other therapies, and I hadn’t healed naturally in seven years.


I realize that, for the first time in seven years, I have no back pain.

Then I drive from New York to Maine. Long drives were always my Kryptonite, and sure enough, by the third hour of the six-hour ride, I can feel my old pain begin to return. I try not to think about it, but it is there. I feel defeated, and I call Berman a few days later. He tells me to stay positive. “Sometimes it will come back a bit and then go away again,” he says. “You just have to give it some time.”


Slowly, the pain subsides. While it pops up every now and again, it disappears just as quickly. Then, about three months after my treatment, it seems destined to never return, no matter how long I drive or how much I exercise. It’s just gone.


At this point, it’s been nearly a year, and I’m pain-free. Still, I worry that it’s all just temporary. I recently heard from Lamon Brewster, the boxer. He said his recovery had inexplicably failed, leaving him blind in his left eye once more. “It just reversed,” he says. While Brewster is the exception and not the rule among the SVF patients I’d spoken with, his case is an important reminder of something I try not to think about too much: When you sign up to be a guinea pig, nothing is certain, and only time will tell




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