Scientists at the Yerkes National Primate Research Center at Emory University in Atlanta have used stem cells derived from the dental pulp of monkeys to stimulate the generation of neural cells in an animal model. Such an achievement offers hope for people who are afflicted with diseases of the central nervous system, such as Parkinson’s and Hungtington’s diseases, among others, as well as for those people who suffer from spinal cord and traumatic brain injuries.

Anthony Chan, DVM, Ph.D., assistant professor of human genetics at Emory’s School of Medicine, led the experiments. Dr. Chan and his colleagues took stem cells which they had derived from the dental pulp of a tooth of a rhesus macque, and transplanted the stem cells into the hippocampal areas of the brains of mice. The stem cells were then found to stimulate the new growth of neurons and other types of specialized neural tissue.

According to Dr. Chan, “By showing that dental pulp stem cells are capable of stimulating the growth of neurons, our study demonstrates the specific therapeutic potential of dental pulp stem cells and the broader potential for adult stem cells. Being able to use your own stem cells for therapy would greatly decrease the risk of cell rejection that we now experience in transplant medicine.”

Dental pulp stem cells are readily and universally available, as anyone of any age may have his or her dental pulp stem cells isolated during a routine visit to the dentist, thereby allowing for a very convenient type of autologous (in which the donor and the recipient are the same person) stem cell therapy.

Researchers from the biotech company ImmunoCellular Therapeutics (IMUC), Ltd., have presented data demonstrating that an immunological response is generated against cancer stem cells that are derived from a specific type of brain cancer known as glioblastoma.

Some types of cancer have been found to develop from their own unique type of cancer “master” or stem cells, and now a new type of cancer therapy may be possible by targeting the destruction of these cancer stem cells.

The cell surface marker CD-133 is found to be present on many different types of cancer stem cells and is therefore an excellent target for ICT-121, which is the name of IMUC’s proprietary cancer stem cell vaccine and which is specifically designed to generate a T-cell response against CD-133. Cancer stem cells which are CD-133-positve are perpetually self-renewing and notoriously resistant to standard therapies such as chemotherapy and radiation. As such, these cancer stem cells are highly tumorigenic and metastatic. An immunotherapy such as ICT-121, which targets the cancer cells at their point of origin and source, namely, while they are still in their earliest and most primitive stage, may be effective in destroying the cancer cells and stopping their proliferative ability.

John Yu, M.D., founder, chairman of the board of IMUC, and co-inventor of the ICT-121 technology, presented the company’s data over the weekend at the International Society for the Biological Therapy of Cancer (iSBTC) Conference in San Diego. According to Dr. Yu,

Scientists in Nagoya, Japan have demonstrated the important role that endogenous adult stem cells play in angiogenesis, which is the formation of new blood vessels. The study was led by Dr. Kazuhisa Kondo, who showed that “adipose-derived regenerative cells” (ADRCs) mobilized endogenous progenitor cells to enhance angiogenesis in a mouse model of critical limb ischemia.

Previous animal studies and human clinical trials have demonstrated that neovascularization is inducible by exogenous stem cell transplantation into ischemic muscle, with one clinical trial also demonstrating that human patients with critical limb ischemia respond to exogenous adult stem cell therapy not only with an increased systemic production of chemokines but also with the mobilization of endogenous CD34 stem cells from their bone marrow. It remained unknown, however, whether the resulting angiogenesis was caused directly by differentiation of the exogenous adult stem cells into the newly formed endothelial cells, or indirectly by an interaction between the cytokines and the recipient muscle. A study conducted by Dr. Keith March in 2004 also demonstrated that angiogenesis is mediated via cytokine secretion, although the exact extent of this mediation remained to be determined. Now, Dr. Kondo and his colleagues have demonstrated that the neovascularization which they observed in a mouse model of critical limb ischemia was directly dependent upon the mobilization of endogenous progenitor cells from the bone marrow.

After isolating ADRCs from the adipose tissue of mice in which hind-limb ischemia had been induced, Dr. Kondo and his team then expanded the ADRCs and transplanted them back into the ischemic tissue of the mice. Those mice which received the ADRCs showed a greater laser Doppler blood perfusion index and a higher capillary density when compared to the control mice. Additionally, the ADRCs were also found to increase circulating progenitor cells through the chemokine SDF-1 (stromal cell derived factor). Additionally, the administration of the systemic antibody to SDF-1 by intraperitoneal injection resulted in a blocking of the mobilization and efficacy of the adipose stem cells to induce angiogenesiis, through a mechanism by which the anti-SDF-1 neutralizing antibody caused a reduction in the number of circulating endogenous progenitor cells. Such a discovery highlights the central role that SDF-1 plays in facilitating the mobilization of endogenous progenitor cells.

Dr. Kondo’s study has important practical implications, since most people are not eager to have holes drilled in their bones for the harvesting of autologous stem cells from bone marrow. By contrast, adipose-derived stem cells now present an alternative source to autologous stem cell therapy, since the derivation of stem cells from fat is simpler than that from bone marrow. In fact, several companies such as Cytori have patents on self-contained closed systems by which adipose mononuclear cells are quickly and easily purified at the point-of-care.

As Dr. Kondo’s study indicates, the dynamics of therapeutic angiogenesis involve complex chemical and molecular interactions between the transplanted exogenous populations and endogenous stem cell reserves. In the stimulation of angiogenesis, adipose-derived adult stem cells offer a promising therapeutic modality, especially as a treatment for severe ischemic disease. Additionally, the chemokine SDF-1 is now recognized as playing a fundamental role in mobilizing endogenous progenitor cells.

Dr. Kazuhisa Kondo and his colleagues are in the Department of Cardiology at the Nagoya University Graduate School of Medicine and the Department of Bioengineering Sciences at the Nagoya University Graduate School of Bioagricultural Sciences.

The U.S. biotech company Harvest Technologies has received Investigational Device Exemption (IDE) from the Food and Drug Administration (FDA) to conduct the first randomized, double blind placebo controlled clinical trial in the U.S. in which autologous adult stem cells will be used to treat patients with end-stage critical limb ischemia (CLI).

CLI is the terminal stage of peripheral artery disease (PAD), for which the only treatment is usually amputation, which carries a high risk of mortality. Now, however, adult stem cells offer the possibility of a new form of treatment for CLI, by which the diseased tissue of the affected limb could be regenerated, thereby sparing the limb from amputation.

This “feasibility trial” will enroll 48 patients who are at extreme risk of amputation, having exhausted all surgical and procedural options and who will be treated with their own autologous (in which the donor and the recipient are the same person) adult stem cells derived from their own bone marrow and prepared with the company’s proprietary BMAC (Bone Marrow Aspirate Concentrate) System which is a point-of-care device that concentrates a patient’s own adult stem cells from their own bone marrow in approximately 15 minutes at the bedside. The stem cells will then be injected directly into the affected limb in an effort to induce angiogenesis (blood vessel formation) and thereby rescue the limb from the necessity of amputation.

Based in Plymouth, Massachusetts, Harvest Technologies is the first company to offer clinicians a simple and easy-to-use point-of-care method for concentrating and preparing stem and precursor cells from a small aspirate of autologous bone marrow in just 15 minutes through its BMAC bone graft applicators, which facilitate the premixing of bone graft materials with bone marrow aspirate concentrate. Unlike previous studies that have been conducted in which more complicated methods were used for processing and concetrating adult stem cells from a patient’s bone marrow, the BMAC graft delivery pack streamlines and expedites both the preparation and the ultimate delivery of the graft composite to the surgical site.

Harvest Technologies is also providing a patient-education website for individuals participating in the clinical trial, and their referring physicians, at www.CLIclinicalstudy.com, where information on the study and the science underlying it is now available. The clinical trial is being led by Principal Investigator Mark D. Iafrati, M.D., Chief of Vascular Surgery at Tufts Medical Center in Boston, and the CLI study is also enrolling subjects at participating locations in South Carolina, Houston, Florida, and New York.

One of the world’s leading authorities on stem cells is quitting the UK for a more balanced and fair scientific environment in France. Dr. Colin McGuckin, professor of regenerative medicine at Newcastle University, announced this week that he is relocating his entire laboratory and staff to France, claiming that there is insufficient support for adult stem cell work in the United Kingdom.

“You would barely know adult stem cells exist”, says Dr. McGuckin, in reference to the unfairly biased environment that exists in the UK, in which the immediate benefits of adult stem cells, which are already being realized in clinics today, are ignored while most attention is instead given to the vague and remote possibility of uncertain future benefits from embryonic stem cells, which would not be attainable until after another decade or more of research, if such benefits are attainable at all.

Dr. McGuckin is the UK’s leading specialist in stem cells of umbilical cord blood origin, having pioneered the method of derivation for these stem cells in 2005. Since then he has been successful in regenerating various types of tissue from umbilical cord blood stem cells, including liver tissue which is one of the most highly specialized and complex types of tissue in the human body. Despite such success, however, his pioneering work has not received as much attention in his homeland as has embryonic stem cell research, to the dismay of many scientists. Not only to Dr. McGuckin but to many other stem cell experts, the unjustified prioritization of embryonic stem cell research above adult stem cell work is a serious issue, especially in light of the fact that adult stem cells have already been used in the clinic with immediate benefits to patients, while embryonic stem cells have proven to be highly problematic in the laboratory and have never advanced beyond the laboratory stage precisely for that reason. By sharp contrast to adult stem cells, embryonic stem cells have never been used to treat anyone for anything, and any possible clinical viability of embryonic stem cells is at least another decade away, if not farther, if such a viability is achievable at all.

Because of such an unfavorable scientific atmosphere in the UK, Dr. McGuckin plans to leave Newcastle University for France where he will reestablish himself at the University of Lyon in January. In addition to his entire laboratory, Dr. McGuckin will also be bringing his research team of approximately ten other scientists with him to France, including Dr. Nico Forraz, another leading stem cell expert. After the relocation to Lyon, Dr. McGuckin and his colleagues will open the world’s largest institute devoted first and foremost to umbilical cord blood and adult stem cell research.

Although adult stem cells are often cited as being ethically and politically noncontroversial, since embryos are not destroyed in the extraction of adult stem cells, it is primarily for scientific reasons that adult stem cells are so successful in treating a wide variety of diseases, while embryonic stem cells are thus far completely unsuccessful in treating anything. Ethics and politics aside, adult stem cells and embryonic stem cells behave very differently from each other, and it is purely because of the scientific nature of these cells, not because of politics or ethics, that adult stem cell therapy is already a clinical reality with immediate benefits, whereas embryonic stem cells are not yet clinically viable and any therapeutic potential which embryonic stem cells might ever possibly offer will require at least another decade of technological advancement, if not more, before embryonic stem cells could even be considered as a clinical therapy. Meanwhile, there are many patients who cannot wait another decade before being treated for their various diseases or injuries, and such patients can benefit from adult stem cell therapy today.

Pointing out that his primary professional obligation is toward the treatment of his patients, Dr. McGuckin states, “The bottom line is that my vocation is to work with patients and help patients and unfortunately I can’t do that in the UK.” France, however, offers “a much better environment to cure and treat more people”, and “a much more reasoned balance” between adult and embryonic stem cell research. Many researchers agree with Dr. McGuckin that in the UK there is an irrational over-emphasis on embryonic stem cell research to the detriment of all else. As Dr. McGuckin states, France “is very supportive of adult stem cells because they know that these are the things that are in the clinic right now, and will be more likely in the clinic. A vast amount of money in the UK from the government has gone into embryonic stem cell research with not one patient having been treated, to the detriment of adult stem cells, which have been severely underfunded.”

Indeed, this is not the first time that the UK has forced a leading stem cell scientist to leave for another country. In 2006, Dr. Miodrag Stojkovic also decided to quit the UK, taking his laboratory and adult stem cell research team to Spain. Consequently, Dr. McGuckin, Dr. Stojkovic and many others are critical not only of UK academics in general, but also of Parliament and the media in the UK, for the unjustified attention that is consistently given to embyronic stem cells at the deliberate and systematic exclusion of adult stem cells.

In addition to suffering from a lack of laboratory space in the UK, Dr. McGuckin says he has been forced to decline an investment offer of 10 million pounds due to a lack of receptivity and organization on the part of Newcastle University. He also states that he has been forced to put more than 1.8 million pounds of grant funding on hold because of insufficient space and facilities in which to conduct the work. According to Dr. McGuckin, “I kept getting told our situation would get better, but it never did.”

Although the pro vice-chancellor for the faculty of medical sciences at Newcastle University, Chris Day, has expressed surprise over Dr. McGuckin’s concerns, and despite disagreement over some of Dr. McGuckin’s claims from organizations such as the UK National Stem Cell Network, many other researchers agree with Dr. McGuckin that there is currently a research environment in the UK which is unjustifiably and irrationally biased in favor of embryonic stem cell research, and that this bias must change toward “more balanced research.” According to Dr. Anthony Hollander, professor of rheumatology and tissue engineering at the University of Bristol, “We desperately need more funding for adult stem cell research because with these cells we really can make a difference to patients’ lives, and we can do it now, not in ten years time as is promised for embryonic stem cells.”

According to the group known as “Comment on Reproductive Ethics” (CORE), the loss of Dr. McGuckin would create a “huge hole” in Newcastle’s research portfolio.

Scientists at the University of Michigan have discovered that four genes which were already known to be involved in the control of cancer are also actively involved in the aging process and in stem cell regulation. The four genes, which are known to suppress tumor formation, also regulate the ability of endogenous adult stem cells to replace worn out tissue. When a person’s own adult stem cells fail to replace such tissue, the aging process occurs.

As cells age, these four genes switch on and off in a coordinated fashion in order to reduce the risk of cancer, although such a process also hinders the capacity of stem cells to regenerate tissue. The findings illuminate the shared genetic pathways between natural stem cell regeneration, aging and cancer.

According to Dr. Sean Morrison, director of the University of Michigan Center for Stem Cell Biology, “All four of these genes had been implicated in the regulation of cancer, but only one of them had been implicated in the regulation of stem cells and aging. So this is a pretty significant expansion of our mechanistic understanding of the connections between these vital processes.”

Commenting on the three-year study of mouse brain cells which led to the discovery, Dr. Morrison added, “The genes identified in this study work together to reduce the function of adult stem cells as they age. Embryonic stem cells offer the advantage of not aging, not turning on this pathway.” In order to use embryonic stem cells as an actual medical treatment for something, however, the embryonic stem cells would have to undergo a certain degree of differentiation, which would therefore involve the aging of cells and the activation of these four genes. Meanwhile, the point is somewhat irrelevant at least for the foreseeable future since embryonic stem cells have never been used as a clinical therapy to treat any disease or injury, and the likelihood of embryonic stem cell technology advancing to the stage of a safe and effective clinical therapy is at least another decade away, if not further, by unanimous scientific consensus. By sharp contrast, adult stem cells have already been proven to be a viable treatment modality and have already been used in a wide range of clinical settings to treat a vast array of medical conditions for many years.

Specifically, the four genes under consideration are Ink4a, Arf, Hmga2 and let-7b, which were examined in this particular study by breeding mice that lacked combinations of these genes, and then measuring the effects of the missing genes on stem-cell function and brain-cell formation at different life stages. According to Dr. Jinsuke Nishino, a postdoctoral fellow in Dr. Morrison’s lab, “We have now identified an entire pathway that changes gene expression within stem cells as they age, and that helps to explain why old tissues have less stem-cell function and less regenerative capacity.”

In a 2006 publication in Nature, Dr. Morrison and his colleagues demonstrated that the Ink4a gene, which was already understood for its role as a tumor suppressor, becomes increasingly active with age, not only in the suppression of tumors but also in the suppression of stem cell replication, at least in mouse models. At that time, however, no one understood what it was exactly that causes Ink4a to become increasingly active with age. Now, Dr. Morrison and his colleagues have demonstrated that the activity of Ink4a is regulated by Hmga2, which in turn is controlled by let-7b. In light of these recent findings, the ability of the Ink4a gene to become activated with age would appear to be a type of defense mechanism against cancer-causing genetic mutations, which accumulate with the repeated cell division that is associated with aging. Although the studies were conducted with mice, the same molecular processes are believed to be at work in humans, who also possess the same four genes.

As Dr. Morrison explains, “The tumor-suppressor mechanisms ramp up with age. And the good news is that it allows us to get older before getting cancer. The bad news is that your tissues lose their regenerative capacity, making you older. The more we study this issue, the more we think that tissue aging exists as a by-product of mechanisms that were created to protect us against cancer.”

As scientists understand more and more about the cellular, molecular and genetic processes of life, such discoveries will no doubt play a major role not only in the suppression and treatment of diseases such as cancer, but also in the development of increasingly precise medical tools, such as stem cells.