Stem cells in the Brains of Crayfish

Ayub et al. Dev Neurobiol.

Stem cells have been found in various organs to participate in repair after injury. For example, after a heart attack, cardiac specific stem cells that reside in the atrium are known to proliferate and cause repair of damage. In the brain stem cells participate in a variety of processes, for example stem cells in the dentate gyrus multiply in people who are mentally active. These cells appear to have reduced function in patients of depression. Interestingly, in depressed patients anti-depressants have been demonstrated to increase stem cell activity.

In a recent study (Ayub et al. Environmental enrichment influences neuronal stem cells in the adult crayfish brain. Dev Neurobiol. 2010 Dec 29) the effect of environmental stimulation on brain stem cells in crayfish was studied.

The scientists found that new brain stem cell development occurred in sexually differentiated procambarid crayfish by environmental enrichment. The studies also showed that environmental enrichment increases the cell cycle rate of neuronal stem cells. There was no effect of environment on the overall numbers of cells circulating in the hemolymph, enrichment resulted in increased expression of glutamine synthetase, a marker of the neuronal stem cells, in a small percentage of circulating cells; there was little or no expression of this enzyme in hemolymph cells extracted from deprived animals.

These data suggest that there seems to be a correlation between brain activity and brain stem cell activity in a variety of animals as well as in humans. By identifying chemical signals that control brain stem cell activity, it may be possible to develop “brain enhancing drugs”. One approach that has been attempted to do this is through administration of human chorionic gonadotrophin. This hormone is associated with pregnancy and is believed to be responsible for the pregnancy-associated neurogenesis that occurs in pregnant human women and mice.

While a study in stroke patients using human chorionic gonadotrophin did not demonstrate astonishing results, it may be possible to use this agent in more chronic situations of neurodegeneration such as Parkinson’s or Alzheimer’s disease.

Enhancing Efficacy of Bone Marrow Transplant

Huang et al. Blood. [Epub ahead of print]

Bone marrow transplantation has cured many patients of hematological diseases such as leukemias and lymphomas. Additionally, bone marrow transplantation is becoming used more and more in treatment of autoimmune diseases such as type 1 diabetes and multiple sclerosis. Unfortunately, there are still numerous limitations to this procedure. One of the biggest ones is that occurrence of graft versus host disease, in which the transplanted stem cells produce immune cells that attack the recipient. The other major problem is graft failure, in which the transplanted stem cells do not “take”.

The group of Dr. Ildstad from the University of Louisville has been working on enhancing bone marrow transplantation by co-administration of other cells called “facilitator cells.” In a recent publication (Huang et al. CD8{alpha}+ plasmacytoid precursor DC induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo. Blood. 2010 Dec 29) it was shown that a type of dendritic cell, called the plasmacytoid dendritic cell, is capable of promoting bone marrow transplant efficacy through stimulation of T regulatory cells.

The scientists demonstrated that after bone marrow transplant from mismatched donors, there are immune suppressive cells, called T regulatory cells, that develop under specific conditions that stop the new (donor derived) immune system cells from attacking the recipient. When a mismatched bone marrow transplant is performed together with plasmacytoid dendritic cells, these cells “instruct” the donor immune system to generate T regulatory cells, which prevent graft versus host disease.

Implications of this research may be profound in areas outside of bone marrow transplantation for leukemias. In solid organ transplants, patients are required to take life-long immune suppressants to prevent the transplanted organ from being rejected. If donor bone marrow transplantation is performed with the donor organ, then the body does not reject the organ. Unfortunately this is not possible because bone marrow transplantation has a high risk of graft versus host disease. If the discovery of Dr. Ilstad’s group can be translated to humans, it may be possible to induce “immunological tolerance”, which is a state of immune un-responsiveness to the transplanted organ, while maintaining a functioning immune system towards pathogens and bacteria.

Resveratrol Suppresses Cancer Stem Cells

Pandey et al. Breast Cancer Res Treat.

Resveratrol is a compound found in grapes, red wine, purple grape juice, peanuts, and berries that has been associated with many health benefits, particularly reduction in heart disease. Some studies have demonstrated that resveratrol increases life span when administered at high concentrations. One area of controversy has been the potential of resveratrol in the treatment of cancer.

One way of testing the anti-cancer efficacy of compounds is to administer the compound of interest to cancer cells that are growing “in a test tube”, or “in vitro.” Recently it was shown that cancer cells taken from a patient and propagated in vitro are usually not representative of the original tumor from which the cancer cells were excised. Specifically, it has been shown that in patients, cancer cells can broadly be classified into the rapidly multiplying cells, and the “sleeping cells” otherwise known as tumor stem cells. It appears that in vitro the rapidly multiplying cells continue multiplying, but the cancer stem cells do not multiply. This is important because the cancer stem cells seem to be the cells responsible for causing the tumor to spread, whereas in the rapidly multiplying cells actually seem to be weaker and more sensitive to chemotherapy.

To date the majority of studies investigating effects of resveratrol on cancer have focused on testing with the rapidly multiplying cells. The paper published today investigated the effects of resveratrol on tumor stem cells. Breast cancer tumor stem cells where isolated based on expression of the proteins CD44 and ESA, and lacking CD24. Tumor stem cells were harvested from patients that were both estrogen receptor positive and negative. It was found that addition of resveratrol caused death of the tumor stem cells, as well as blocked their ability to form three dimensional tumors in tissue culture called “mammospheres.”

Interestingly it seemed like the effects of the resveratrol were mediated by manipulating the way in which the cancer stem cells make fat. Specifically, resveratrol caused a significant reduction in fat synthesis which is associated with down-regulation of the enzyme fatty acid synthase (FAS). The suppression of the enzyme FAS was correlated with upregulation of the genes DAPK2 and BNIP3, which are known to stimulate a process called “apoptosis”, or cellular suicide.

This recent paper belongs to a growing example of scientific reports in which various “treatments” advocated by naturopathic doctors seem to have effects on cancer stem cells. For example, a previous publication (Kakarala et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat. 2010 Aug;122(3):777-85.) reported that the chemical curcumin, which is a component of the Indian spice turmeric, selectively inhibits cancer stem cells.

It appears that many of the chemotherapeutic drugs that are conventionally used in the treatment of cancer do not affect the cancer stem cell because chemotherapy requires tumor cells to be actively proliferating. In contrast, many of the “natural remedies” seem to suppress cancer stem cells because their activities seem to be mediated by other means than the ones in which chemotherapy works. It will be interesting to see if more papers such as the present one appear, which seem to provide scientific rationale for a more “compassionate approach” to cancer therapy

Increasing Efficacy of Stem Cell Therapy for Spinal Cord Injury

Jin et al. Spine (Phila Pa 1976).

Clinical trials of stem cells for treatment of spinal cord injury are currently being conducted in the United States and abroad. For example, the Covington Louisiana company TCA Cellular Therapy LLC is recruiting 10 patients with spinal cord injury to receive intrathecal infusion (lumbar puncture) of autologous, ex vivo expanded bone marrow-derived mesenchymal stem cells. Completed clinical trials have demonstrated some rationale that stem cells may be useful. For example, Kumar et al. (Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: A phase I/II clinical safety and primary efficacy data. Exp Clin Transplant. 2009 Dec;7(4):241-8) reported on 297 spinal cord injury patients that were treated with their own bone marrow cells injected intrathecal. 33% of the patients reported an objective improvement.

As with other clinical trials of stem cell therapy, it appears that in the area of spinal cord injury there still remains room for improvement. We at Cellmedicine have reported a stunning improvement in a spinal cord injury patient by using a combination of CD34 and mesenchymal stem cells, which was recently published http://www.intarchmed.com/content/pdf/1755-7682-3-30.pdf. Unfortunately this was only one patient and more studies are required.

In an attempt to improve efficacy of stem cell therapy for spinal cord injury, a group from the Department of Neurosurgery, Spine and Spinal Cord Institute, at the Yonsei University College of Medicine, Seoul, Republic of Korea, has created an artificial method of increasing growth factor production from stem cells of the nervous system called neural progenitor cells. Previous studies have shown that neural progenitor cells are capable of treating several models of spinal cord injury, however their effects appear to be transient. Vascular endothelial growth factor (VEGF) is a protein that increases blood vessel production in tissues and has been previously demonstrated to stimulate integration of nervous system cells after spinal cord injury. Since increasing VEGF production could hypothetically increase efficacy of neural stem cells, a series of experiments were performed in order to generate modified neural stem cells which have enhanced VEGF production.

It is known that insertion of a gene into a cell can cause the cell to produce the protein made by the gene. So theoretically all the researchers had to do is to transfect (insert) the VEGF gene into the neural stem cells and the neural stem cells would be more effective. The problem with this is that too much VEGF can have negative effects. A more attractive approach would be to program the progenitor cells in such a manner so that they produce VEGF only when it is necessary. During spinal cord injury, the area of damage is associated with reduced oxygen, a condition called hypoxia. Ideally one would want to engineer the stem cells in a manner so that they produce VEGF only during times of hypoxia. One way of doing this is to control the expression the gene by using an inducible promoter.

Promoters are pieces of DNA that control expression of genes that are in front of them. Some promoters always turn on gene expression (these are called constitutive promoters), others turn on expression only under specific conditions (these are called inducible promoters. The promoter that turns on erythropoietin is an inducible promoter. Erythropoietin is made by the kidney and stimulates production of red blood cells. Its expression is turned on under conditions of lack of oxygen. This is why people who live in high altitudes have higher expression of erythropoietin. The scientists in the current publication developed a genetically engineered neural stem cell that contains the VEGF gene under control of the erythropoietin promoter. What this means is that the cells will be producing VEGF only under conditions of hypoxia. In order to selectively detect the areas of hypoxia, the scientists also developed stem cells that have the luciferase gene in front of the erythropoietin promoter. Luciferase is a protein that generates light and allows for easy detection in vitro and in vivo of the hypoxic cells.

The scientists found that the stem cells administered during hypoxia generated significantly higher concentrations of VEGF, which was associated with the promoter being turned on, as assessed by luciferase expression. Furthermore, rats receiving the VEGF expressing stem cells possessed a significantly lower amount of nerve damage and higher ability to recuperate after spinal cord injury.

These data suggest that it is feasible to combine inducible promoters with stem cells in order to augment various activities of the stem cells. This concept could be applied to numerous settings. For example, mesenchymal stem cells are known to selectively migrate to areas of inflammation. In the setting of cancer, mesenchymal stem cells could be transfected with genes that are encoding toxic substances. This way chemotherapy could be targeted only to cancer cells and therefore have a better safety profile.

Gene therapy has failed to a large extent because of lack of ability to control where the genes are administered. It may be possible that advancements in stem cell technologies will allow for a rebirth of gene therapy in that the stem cells may be used to deliver genes only to the tissues where they are needed.

Time to end stem cell institute CIRM

Wesley J. Smith , San Francisco Chronicle

The California Institute for Regenerative Medicine (CIRM) was created in 2004 as a result of the California Proposition 71, which called for a new bond issue to generate 3 billion dollars in order to support stem cell research in the State. In part, the institute was created as a response to President George W. Bush’s order restricting federal funding of embryonic stem cell research. The hope behind this enormous influx of cash to stem cell research was based on the popular belief that the State would have reduced medical costs, as well as treatments for many of the debilitating diseases that could benefit from stem cell therapy.

According to the author of the article, who is a senior fellow at the Discovery Institute’s Center on Human Exceptionalism and a consultant to the Center for Bioethics and Culture. “The CIRM hasn’t come close to fulfilling those promises. Here’s why California voters should reject the bond issue and shut the agency down in 2014…”

His rationale is that a) CIRM was created primarily to fund human cloning for research and embryonic stem cell research. So far, cloning has failed and embryonic stem cell cures, if they ever come, are a very long way off; b) Questionable uses of taxpayer’s funds. Specifically, $300 million went to help pay for plush research facilities, particularly those associated with board members of CIRM; c) Members of CIRM are paid exorbitant salaries. For example, the head of CIRM makes just under $500,000 a year, Art Torres, a board member and former chairman of the California Democratic Party, works four days a week – for a whopping $225,000 a year.

It is our opinion that basic research is critical for development of new therapies and for advancement of medicine. Therefore, conceptually, there is nothing wrong with supporting the use of taxpayer’s dollars for stem cell research. The issue that we have revolves around what research gets funded and how those projects are in line with the goals for which the funds were donated.

In the “drug development cycle” the first step is basic research and discovery of a biological mechanism of action associated with the disease. The second step is understanding how to manipulate the interaction. The third step is developing an intervention that may theoretically be useful and testing it in animal models of diseases. The fourth step, which is considerably more difficult, is to test the putative therapy in humans either at a low dose in healthy volunteers, or in terminal patients. This usually involves 10-40 patients and is formally called a Phase I clinical trial. Phase II clinical trials are the fifth step of developing a therapeutic. This involves 30-100 patients and assesses efficacy of the therapy in patients with disease. The last step of developing a drug involves conducting Phase III clinical trials, whose aim is to see whether the putative therapy induces therapeutic effects in a double blind, placebo controlled manner.

The majority of research funded by CIRM covers projects that are at the first to third steps, that is, from identifying new biological pathways, to trying to treat mice. Very few CIRM funded projects supported adult stem cell companies that are using their cells to treat patients. We anticipate that with more articles such as the one published by Wesley Smith, CIRM will become more cognizant of the reason why taxpayers supported the Institute: to develop cures faster. Indeed, one can see this increasing support in CIRM for adult stem cell companies in that in October of this year only 5 of 19 grants were for embryonic stem cell research.

International Stem Cell Corporation Expands Sales of Skin Care Product

North County Times – McClatchy-Tribune Information Services via COMTEX

The Oceanside California company International Stem Cell Corporation, (ISCO.OB) announced increased sales of its skin care product, the Lifetime Skin Care Line, which was associated with a 19% rise in stock price. In a press release, International Stem Cell Corporation stated “products are now being sold to subscribers of the investment newsletter of John Mauldin, founder of Millennium Wave Investments. The products were earlier offered to investors and others associated with International Stem Cell.”

The company has been developing a novel type of stem cell, called “parthenogenic derived” stem cells that has no ethical issues, yet appears to possess many of the properties associated with embryonic stem cells. Specifically, parthenogenic derived stem cells are generated by “activating” a human egg cell in absence of sperm. These cells multiply like embryonic stem cells, and possess the same ability as embryonic stem cells to generate all tissues of the body. The main therapeutic goals of the company are to develop islet cells for patients with diabetes, hepatocytes for patients with liver failure, and artificial corneas. However, given that approval from the FDA and other regulatory agencies is a long-term process, International Stem Cell Corporation has decided to leverage existing technologies into generating a product that can produce revenue without long-term research and development expenses.

By concentrating extracts that are produced by the parthogenic derived stem cells, the company has created stem cell-based products that are believed to be useful in skin care and restoration. On December 1st 2010, International Stem Cell Corporation announced the launch of its skin care product line which consists of a defensive Day Moisture Serum, and Recovery Night Moisture Serum.

“Because the quality products Lifeline Skin Care offers are experiencing strong demand and the human stem cell extracts require innovative manufacturing processes, we chose to develop our sales channels gradually and incrementally,” said Lifeline Skin Care CEO, Dr. Ruslan Semechkin.

International Stem Cell Corporation has historically been keen to develop products to market in order to generate ongoing revenue while its flagship products are under development. An example of this is the LifeLine research reagents company, which was developed by International Stem Cell Corporation as a means of selling products to researchers that are created as part of the company’s ongoing research and development program.

Stem Cell Transplant Cures HIV in “Berlin Patient”

Huffington Post

Timothy Ray Brown, also known as the “Berlin Patient,” received a bone marrow stem cell transplant in 2007 as part of a lengthy treatment course for leukemia. What was unique about Mr. Brown was that he was HIV positive. He now is HIV negative.

In the December 8th issue of the journal Blood, a scientific paper by Dr. Kristina Allers (kristina.allers@charite.de) entitled “Evidence for the cure of HIV infection by CCR532/32 stem cell transplantation” provided data documenting what is believed to be the first case of a human being cured of HIV by stem cell transplant.

HIV is known to kill patients by depleting an essential component of the immune system called the CD4 T cell. This cell is called the “helper cell” because it coordinates the antibody and cytotoxic arms of the immune response. HIV infection replicates within the CD4 cells and causes their death. Once patients lose their CD4 T cells they become highly susceptible to infections, which eventually results in their death.

Entry of the virus into CD4+ cells requires interaction with a protein called a “cellular receptor”. The main receptor by which HIV enters T cells is the CD4 protein. It was subsequently discovered that a second receptor is needed for the virus to enter, this second receptor can be either a protein called CCR5 or CXCR4. The importance of this “coreceptor” is that some people who are resistant to HIV infection have a different genetic make-up of the coreceptor which does not allow HIV entry. Molecular analysis of these people revealed that the specific CCR532/32 subtype was associated with resistance.

In bone marrow transplantation, the blood making stem cells (hematopoietic stem cells) of the recipient are destroyed by high dose chemotherapy/radiation, and new stem cells from the donor are administered. Theoretically, if the donor possesses the “resistance gene”, then the recipient should end up with CD4 T cells that are resistant to HIV infection.

In the recently published paper, doctors from the Charite Hospital in Berlin report the continued follow-up of the “Berlin patient”. The authors previously reported that the patient was HIV-infected but viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with stem cells from a donor containing the resistance-associated CCR532/32 mutation. It was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the current report the doctors demonstrated successful reconstitution of CD4+ T cells throughout the body, as well as in the gut mucosal immune system following the stem cell transplantation, while the patient remains without any sign of HIV infection.

Interestingly, despite the fact that the patient appeared to be negative for HIV, a high proportion of activated memory CD4+ T cells were observed. These cells are known to be extremely sensitive to HIV infection. Furthermore, they demonstrated that during the process of the immune system re-establishing itself, they found evidence for the replacement of long-lived host tissue cells with donor-derived cells. The authors conclude by stating that “our results strongly suggest that cure of HIV has been achieved in this patient.”

While this protocol is theoretically useful for the cure of HIV, the major drawback is that there is a severe shortage of bone marrow donors in general, and specifically donors that have the HIV-resistance mutation. For this reason, companies such as Benitec, are using genetic engineering technologies in order to artificial produce such mutations. Under this scenario cells are taken from the bone marrow of an infected patient, stem cells are purified, and transduced with genetic material that artificially-cause this mutation.

Stem Cell Institute in Panama Collaborates on New Method of Treating Diabetes-Associated Heart Disease

Zhang et al. Journal of Translational Medicine

Diabetes is associated with numerous “secondary complications” including premature heart disease, renal failure, critical limb ischemia (an advanced form of peripheral artery disease) and diabetic retinopathy. One of the common features of these secondary complications is that they are all associated with low levels of circulating endothelial progenitor cells. We have previously discussed the interaction between inflammation and low levels of circulating endothelial progenitor cells http://www.translational-medicine.com/content/7/1/106. It appears that the uncontrolled sugar levels in the blood cause generation of modified proteins, which initiate low level, chronic inflammation. One of the major mechanisms by which sugar- modified proteins induce inflammation is by stimulating a molecular signaling protein called Toll like receptor (TLR)-4. Generally TLR-4 is used by the body to sense “danger”, that is, to sense pathogens, tissue injury, or various factors that may negatively affect the well-being of the host.

In a collaborative study between Stem Cell Institute Panama, Medistem, and the University of Western Ontario, Canada, it was observed that TLR-4 is associated with induction of heart cell (cardiomyocyte) death in diabetic animals. The scientists demonstrated that suppressing the gene encoding for TLR-4 resulted in prevention of heart disease. The results were published in the article Zhang et al. Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4. J Transl Med. 2010 Dec 15;8(1):133. TLR-4 is known to recognize bacterial endotoxin, fragments of degraded extracellular matrix, as well as the stress protein HMBG-1.

In the current experiment, mice were made diabetic by administration of the islet-specific toxin streptozotocin. Diabetic mice were treated with double stranded RNA specific to the gene encoding TLR4. It is known that when cells are treated with double stranded RNA, the gene that is similar to the double strand is silenced. This process is called “RNA interference”.

Seven days after mice became diabetic, as evidenced by hyperglycemia, the level of TLR4 gene in myocardial tissue was significantly elevated. This suggested that not only does hyperglycemia activate TLR4, which was previously known, but that expression of this pro-inflammatory marker actually is increased. Indeed it may be possible that triggers of TLR4 actually act in an autocrine manner in order to increase cell sensitivity

In order to determine whether TLR4 was associated with the cause of cardiomyocyte death, animals were administered the double stranded RNA in order to suppress levels of TLR4. When this was performed the level of cardiomyocyte death was markedly reduced. This is an important finding since usually scientists think of TLR4 as a molecule that activates inflammation through stimulation of the immune

The authors conclude by stating that new evidence is presented suggesting that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

The research finding that TLR4 is implicated in death of cardiac cells means that agents that suppress it, such as double stranded RNA, may be useful for incorporation into stem cells in order to make the cardiac cells that are derived from the stem cells resistant to death induced by conditions of stress such as hyperglycemia.

How Inflammation Suppresses Stem Cell Function

Wang et al. PLoS One;5(12):e14206.

Low grade inflammation is well known to correlate with development of numerous disease conditions such as heart failure, kidney failure, and diabetes. It is generally accepted that oxidative stress caused by inflammation is one of the means by which disease evolution occurs. Inflammatory conditions usually generate oxygen free radicals that damage cells and cause the cells of the body to lose function. Importance of reducing inflammation in terms of preventing diseases, such as heart disease, is seen by the beneficial effects of antiinflammatories such as aspirin.

A recent paper (Wang et al. TLR4 Inhibits Mesenchymal Stem Cell (MSC) STAT3 Activation and Thereby Exerts Deleterious Effects on MSC-Mediated Cardioprotection. PLoS One. 2010 Dec 3;5(12):e14206.) suggests that inflammation may actually inhibit the activity of stem cells, and through suppressing the body’s repair processes, causes various diseases to appear.

The mesenchymal stem cell is a type of stem cell found in the bone marrow, fat, heart, and other tissues, that is activated in response to injury and acts to heal damaged tissues. Particularly in the case of heart attacks, it has been demonstrated that administration of bone marrow mesenchymal stem cells causes accelerated healing both in humans and animals. The therapeutic effects of mesenchymal stem cells seem to be mediated by production of growth factors, as well as proteins that support creation of new blood vessels, a process called angiogenesis. Currently several companies are currently developing mesenchymal stem cell based drug candidates including Osiris Therapeutics, Athersys Inc, Mesoblast, and Medistem.

Given the fact that these cells are not a “laboratory experiment” but have actually been used in more than a 1000 patients, understanding conditions that affect their activity, as well as means of making them more effective is important. Inflammatory mediators are believed to influence activity of mesenchymal stem cells, since the protein toll like receptor 4 (TLR4), which recognizes tissue inflammation is found in high concentrations on mesenchymal stem cells. TLR-4 was originally found on cells of the “innate” immune system as a molecule that recognizes “danger signals”.

In order to determine the function of TLR4 on bone marrow mesenchymal stem cells, scientists at Indiana University used mice that have been genetically engineered not to have expression of this protein. Bone marrow mesenchymal stem cells from the mice lacking TLR-4 were demonstrated to function in a similar manner to normal mesenchymal stem cells in the test tube. However when these mesenchymal stem cells were administered to mice after a heart attack, the cells were capable of generating a highly significant improvement in heart function as compared to normal mesenchymal stem cells. The scientists concluded that inflammatory signals “instruct” mesenchymal stem cells to produce less therapeutic factors than they normally would.

These data are very interesting since other reports have suggested that inflammatory mediators actually stimulate mesenchymal stem cells to produce higher amounts of anti-inflammatory factors such as interleukin-10. One of the reasons for the discrepancy may be that inflammation in the context of a heart attack may be different than the inflammatory signals used by other studies.

Stem Cell Institute (Cellmedicine) Successfully Treats Spinal Cord Injury Patient with Adult Stem Cells

Peer-Reviewed Joint Publication between Stem Cell Clinic and American Researchers

Panama City, Panama – The Stem Cell Institute (www.cellmedicine.com) reported today recovery of a spinal cord injury patient that was treated with a unique combination stem cell treatment. The patient suffered a crush fracture of the L1 vertebral body on May 13th, 2008 after a single propeller engine airplane crash. As a result of the crash, the patient had severe neuropathic pain, loss of sexual and bladder function, as well as loss of sensation in the legs.

He was treated on Oct 31-Nov 20, 2008, Jan 21-30, 2009, and July 1-10, 2009 with an adult stem cell protocol. The patient underwent a progressive recovery of sensation, mobility, and sexual and bladder function subsequent to stem cell administration. Currently the patient is capable of walking and neuropathic pain diminished substantially.

“The doctors at the Stem Cell Institute have changed my life. After the accident there was no hope. Now I have a new lease on life.” Said Juan Carlos Murillo Rodriguez, the patient who was treated. “I have recently passed my physical and am flying again as a commercial pilot.”

Details of the scientific rationale for the treatment, as well as protocols and outcomes may be found in the peer-reviewed paper “Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report” which was published in the International Archives of Medicine and is available online at http://www.intarchmed.com/content/pdf/1755-7682-3-30.pdf.

“It is my honor that such a team of internationally recognized opinion leaders in the area of stem cells such as Drs. Amit Patel, Michael Murphy and Thomas Ichim have co-authored this publication.” Said Dr. Jorge Paz Rodriguez, Medical Director of the Stem Cell Institute and co-author of the publication. “By combining our clinical experience with cutting-edge advances in molecular and cellular biology, we believe we have put forth a very innovative protocol that we anticipate will be attempted by other groups.