February 1, 2011 by

Scientists look to stem cells to mend broken hearts

Cardiac medicine has traditionally been associated with innovative procedures that sometimes where considered heretical to the present day dogma. For example, the first heart transplant, the use of the balloon catheter, the introduction of thrombolytics, all met substantial resistance from the “establishment” in their time. It appears that the next revolution in cardiac medicine is the use of stem cells. Aside from the obvious ethical and moral dilemmas surrounding embryonic tissues, the major controversy has been the belief that heart tissue does not repair itself after it has been lost. However, slowly but surely it appears that support behind the use of stem cells for heart conditions is gaining momentum.

One sign of this is the recent announcement that Britain’s leading heart charity, the British Heart Foundation (BHF), launched a 50 million pound ($80 million) research project into the potential of stem cells to regenerate heart tissue and “mend broken hearts”.

“Scientifically, mending human hearts is an achievable goal and we really could make recovering from a heart attack as simple as getting over a broken leg,” said Professor Peter Weissberg, medical director at the BHF.

One example of research in this area being performed in England is the work of Professor Paul Riley of the Institute of Child Health at University College London (UCL) who has identified a natural protein, called thymosin beta 4, that plays a role in developing heart tissue. He said his researchers had already had some success in using this protein to “wake up” cells known as epicardial cells in mice with damaged hearts. “We hope to find similar molecules or drug-like compounds that might be able to stimulate these cells further,” he told reporters at the briefing.

Currently the most advanced type of stem cell therapy for the heart involves administration of the patient’s own bone marrow cells into the area of heart damage after a heart attack. This work, which was performed in England and internationally, seems to suggest that cardiac muscle may be preserved when cells from the bone marrow produce various growth factors that stimulate stem cells that are already existing in the heart.

Other methods of administering stem cells into the heart include direct injection into the heart muscle during bypass surgery. This is performed experimentally in patients with severe angina on the hope that the injected stem cells will provide support for formation of new blood vessels, called collaterals, which are anticipated to increase the blood flow to the heart and thereby reduce angina.

Currently embryonic or fetal derived stem cells have not been used for treatment of heart conditions in humans. Therefore, at least for now, ethical issues do not seem to be a major obstacle to advancement of stem cell medicine for hearts.

Filed Under: Adult Stem Cells, Bone Marrow, Heart Disease, News, Stem Cell Research Tagged With: , , , , ,
January 4, 2011 by

Male-Pattern Baldness Found Rooted in Stem Cells

Amanda Chan, MyHealthNewsDaily Staff Writer

A new discovery regarding the presence of stem cells in males with androgenetic alopecia (male-pattern baldness) has led to hope that the disease may be treatable. It was previously believed that people who suffered from baldness also had a depleted number of hair follicle stem cells, meaning that new hair growth would not be possible. However, this new discovery has shown that the number of stem cells present in bald areas and non-bald areas is equal; the difference is a depleted number of hair follicle progenitor cells.

The implication for this discovery are if scientists are able to coax the present stem cells into developing into hair follicle progenitor cells, they would be able to regrow hair. The only FDA approved baldness treatments; Rogaine and Propecia do not have the ability to regrow cells. Propecia works by inhibiting testosterone’s effect on hair follicles, disrupting its ability to decrease the size of hair follicles.

http://www.livescience.com/health/male-pattern-baldness-stem-cells-110104.html

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
January 1, 2011 by

Study Shows Patient’s Own Stem Cells Help Stroke Recovery: 16 Treated Patients Improve in Comparison to 36 Controls

Lee et al Stem Cells 28:1099
Stroke is caused by blocked circulation to parts of the brain usually as a result of a blood clot. Outcomes of stroke are generally proportional to the length of time the circulation was blocked and to the amount of brain tissue injury and death. Although the introduction of “clot busters” has improved outcomes in these patients, substantially morbidity and mortality still occurs. Numerous pharmaceutical approaches have been attempted in the treatment of stroke, both from the perspective of inhibiting tissue damage, and more recently trying to stimulate regeneration of injured brain tissue. To date clinical progress in this area has been relatively insignificant. In fact, in the pharmaceutical industry the condition of stroke has been referred to as a “graveyard for biotechs”.
One potentially promising treatment for stroke would be to augment the body’s own repair processes through activation of stem cells that are either pre-existing in the body, or through administration of stem cells either directly into the damaged brain tissue or areas associated with the damaged brain tissue. Rationale for this includes observations that stem cells from the bone marrow called endothelial progenitor cells are known to enter circulation in patients with stroke. A study from Dunac et al in France demonstrated that patients who have a higher degree of stem cells in circulation after a stroke have a better neurological outcome in comparison to patients who have lower numbers of circulating stem cells. In rats which are given a stroke experimental by ligation of one of the arteries that feeds the brain, called the middle cerebral artery, administration of human or rat stem cells reduces the size of brain damage, as well as causes regeneration of new neurons. Additionally, animal studies have demonstrated that administration of stem cells causes improved behavior as compared to animals receiving control cells or saline.
One reason why there exists a belief in the field that bone marrow derived cells may be capable of generating new neurons is that in female recipients of bone marrow transplant nerve cells have been found that express the Y-chromosome (Weimann et al. Contribution of transplanted bone marrow cells to purkinje neurons in human adult brains Proc Natl Acad Sci USA 100:2088).
In a recent paper (Lee et al. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28:1099) a group from Korea reported what to date is the largest clinical trial of stem cells in stroke. The investigators used mesenchymal stem cells generated from the bone marrow of the stroke patients. These cells are believed to be capable of generating new neurons, as well as producing growth factors that stimulate the brain to heal itself. Mesenchymal stem cells are currently used in clinical trials in the US and internationally for treatment of graft versus host disease, heart failure, and critical limb ischemia (an advanced form of peripheral artery disease that causes 100-200,000 amputations per year). Advantages of mesenchymal stem cells include: a) ability to be expanded in tissue culture; b) Well-known safety profile; and c) Ability to use between individuals without need for matching.
In the study discussed, the investigators selected 52 patients with a defined type of stroke (non-lacunar infarction within the middle cerebral artery territory). Patients were selected 7 days after the stroke in order to have a standardized level of dysfunction. It was previously published that before 7 days the patient may have a sudden increase or decrease in neurological function, but after 7 days post-stroke the neurological function remains stable.
The investigators extracted 5 ml of bone marrow from 16 patients and expanded the mesenchymal stem cells over a 4 week period. The mesenchymal stem cells were defined as cells expressing the markers CD105 (SH-2) and SH-4. Cells were grown as adherent cells in media containing fetal calf serum. The 16 patients received two administrations of 50 million cells intravenously spread apart by a week.
Patients were followed for an average of 117 weeks, with some patients followed as long as 5-years after the stroke. There was a statistically significant difference in overall survival in the patients that received the mesenchymal stem cells as compared to controls. Specifically, 4 of the 16 patients who received the mesenchymal stem cells passed away during the follow-up period as compared to 21 of the 36 control patients.
In studies of embryonic or fetal stem cells, one of the major concerns is development of tumors. This stems from the fact that administration of embryonic stem cells into immune deficient animals causes tumors called teratomas, and in humans there is at least one documented case of a brain tumor developing in a patient who received fetal derived stem cells. Of the patients administered mesenchymal stem cells, no tumors were detected. This is important because this study has one of the longest follow up periods.
Functional improvements as quantified by the modified Rankin Score were noted in patients receiving stem cells, whereas controls overall suffered a decline in function. Specifically, function was assessed at a median of 3.5 years in the control group and 3.2 years in the mesenchymal stem cell treated group. Function was assessed by doctors where were “blinded” to which patient received stem cells and which patient was in the control group. In the control group 13 of 26 patients had a negative rank, which indicates an improved functional outcome for each patient, whereas 21 patients had a positive rank, which means worse outcome. In contrast, in the treatment group 11 of the 16 patients had a negative rank. The difference between groups reached statistical significance.
In 9 patients of the group that received stem cells, a correlation was studied between the cytokine SDF-1 and functional outcome. Functional outcome was determined both by the modified Rankin score as well as by the Barthel index. A positive correlation was found between levels of SDF-1 at the time of MSC treatment and functional outcome in the patients studied. This protein is known to be involved in recruiting stem cells to the site of injury. Given that in this study the stem cells were administered intravenously and not locally (eg by sterotactic injection), it would be logical that a correlation exist between chemotactic signaling and improved outcome. Currently there are companies such as Juvantis, that are administering plasmids expressing SDF-1 in order to induce homing of endogenous stem cells into cardiac infarcts. It is interesting that the same priniciple may be valid in situations of ischemic stroke. To date no studies have been performed clinically using co-administration of stem cells and SDF-1, however, myoblasts transfected with SDF-1 have been used in a clinical trial in Jordan by the company BioHeart for treatment of heart failure.
One other interesting finding of the study besides lack of ectopic tissue or tumor formation is that no adverse effects were associated with using stem cells grown in fetal calf serum. There has been concern in the literature, particularly the academic literature, that fetal calf serum may induce autoimmunity or sensitization upon second MSC administration. This did not appear to be the case.

Filed Under: Adult Stem Cells, Bone Marrow, News, Stem Cell Research, Stroke Tagged With: , , , , ,
December 29, 2010 by

Mechanisms of a New Stem Cell Mobilizer

Jarcome-Galarza et al. J Bone Miner Res.

It is known that the bone marrow contains three main types of stem cells: a) hematopoietic stem cells, which make blood; b) endothelial progenitor cells, which maintain healthy blood vessels; and c) mesenchymal stem cells, which repair a variety of tissues and are capable of producing high amounts of growth factors. After major tissue injury or trauma all three of the bone marrow derived stem cells leave the bone marrow and enter systemic circulation in an attempt to heal the tissue damage. The original compound that was discovered to “mobilize” bone marrow stem cells was granulocyte colony stimulating factor (G-CSF). Studies in mice with lung injury in the late 1970s demonstrated that a lung-derived protein was capable of stimulating bone marrow to multiply and produce higher numbers of granulocytes. It was not until the late 1980s that scientists started injecting purified G-CSF into animals as a method of increasing the number of circulating stem cells. Why would people want to increase circulating stem cells? Commercially one of the main reasons is associated with the process of bone marrow transplantation. In bone marrow transplantation donors were historically required to undergo the painful procedure of bone marrow extraction, which requires an excess of 20 holes to be drilled into their hip bones. Compounds such as G-CSF could be administered to donors in order to make their stem cells enter circulation, and then the stem cells could be isolated from the blood instead of the bone marrow. This makes the procedure a lot less painful and arguably a lot safer. Additionally, the possibility of mobilizing stem cells by administration of a drug has the possibility of artificially increasing stem cell numbers in patients with degenerative diseases in order to attempt to naturally heal the condition.

The clinical use of G-CSF for mobilization and also for increasing granulocytes in the blood has resulted in multibillion dollars per year in sales for companies such as Amgen. Naturally, this has stimulated much interest in the process of how to make stem cells leave the bone marrow. G-CSF stimulates bone marrow stem cell release through several mechanisms. The main mechanism appears to be associated with stimulation of osteoclasts, which cause modulation of the bone marrow structure and physically release the stem cells from their environment. Other mechanisms exist such as breakdown of stromal derived growth factor (SDF-1). This protein is made by the bone marrow and literally keeps the hematopoietic stem cells stuck to the bone. When the bone marrow levels of SDF-1 decrease, the hematopoietic stem cells are no longer “stuck” to the marrow and as a result enter circulation. Yet another mechanism is that G-CSF activates neutrophils to produce various enzymes that cleave proteins on the bone marrow. These cleaved proteins are then recognized by pre-formed antibodies, which activate complement, which causes small holes in the bone marrow and thus releases stem cells.

The second “stem cell mobilizer” to be approved by the FDA is a drug called Mozibil which blocks the interaction between SDF-1 and its receptor CXCR4. This drug was sold by Anormed to Genzyme in a deal worth more than half a billion dollars. Mozibil is a superior stem cell mobilizer to G-CSF in many patients and as a result has rapidly been implemented clinically. Interestingly, it appears that Mozibil causes redistribution of different ratios of hematopoietic, mesenchymal and endothelial progenitor cells than G-CSF.

One of the most recent mobilizers under development is Parathyroid Hormone. This naturally –occurring substance has been demonstrated in clinical trials to mobilize stem cells, but apparently through a mechanism different than G-CSF and Mozibil. Specifically, both of these drugs appear to cause a temporary depletion of the stem cells in the bone marrow, whereas Parathyroid Hormone seems to preserve the stem cells inside of the bone marrow.

A recent paper (Jacome-Galarza et al. Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow. J Bone Miner Res. 2010 Dec 29) explored the activities of Parathyroid Hormone on osteoclasts in the bone marrow of mice. The authors found that treatment of mice with Parathyroid Hormone for 7 or 14 days increased the number of osteoclastic progenitors in the bone marrow as well as the absolute number of hematopoietic progenitors. These data suggest that the hormone acts not only as a means of stimulating redistribution of hematopoietic stem cells, but also may be involved in directly stimulating their multiplication, possibly through modulating activity of osteoclasts.

Filed Under: News, Stem Cell Research Tagged With: , , , , ,
December 29, 2010 by

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.

Filed Under: News, Stem Cell Research Tagged With: , , , ,
December 29, 2010 by

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.

Filed Under: Adult Stem Cells, Bone Marrow, News, Stem Cell Research Tagged With: , , , ,
December 29, 2010 by

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

Filed Under: Cancer, News, Stem Cell Research Tagged With: , , , , ,
December 29, 2010 by

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.

Filed Under: Adult Stem Cells, News, Spinal Cord Injury, Stem Cell Research Tagged With: , , , , , ,
December 18, 2010 by

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.

Filed Under: News Tagged With: , , , ,
December 3, 2010 by

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.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
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