Dr. Porfirio Hernandez, the Deputy Director of Researchers at the Hematology and Immunology Institute in Cuba, and the main author of a publication entitled, “Autotransplant of Adult Stem Cells in Lower Limb with Critical Ischemia”, has now been awarded with the Dionisio Daza y Chacon prize, granted by the Spanish Magazine of Surgical Research for the best Spanish medical publication of 2007.

After years of conducting laboratory research with animals, Dr. Hernandez and his colleagues began their first adult stem cell clinical trials in 2002, at which time they began using autolgous (in which the donor and the recipient are the same person) stem cell therapy to treat patients who were suffering with peripheral artery disease in their lower limbs.

Similar to the ischemic cardiopathy that is caused by atherosclerosis, and to the cerebrovascular disease that increases the risk of stroke, critical limb ischemia affects the arteries of the lower limbs. Previously, the only form of treatment for the most advanced cases is amputation. Now, however, physicians around the world such as Dr. Hernandez are demonstrating that adult stem cells regenerate ischemic arteries by stimulating angiogenesis in the areas of damaged tissue, thereby restoring proper circulation to the limbs.

Such stem cell techniques are now also being extended to other applications, especially to those maladies that can benefit the most from increased vascularization, such as problems in opthalmology.

Affiliated with Harvard Medical School, the Joslin Diabetes Center is the world’s largest research center and clinic devoted exclusively to the study and treatment of diabetes. Similarly, the Harvard Stem Cell Institute is one of the leading organizations in the world dedicated to scientific collaboration in stem cell biology. Now, researchers from both organizations have discovered that insulin plays a much greater and more important role, in many other physiological processes, than previously realized.

Primarily, insulin is well known for its importance in carbohydrate metabolism, and an insufficiency of insulin in diabetes has been understood for decades to cause a number of life-threatening problems. Additionally, since the 1990s it has been known that insulin inhibits a specific gene regulator protein known as FOXO, which is active not only in diabetes metabolism but also in tumor suppression, in the maintenance of stem cells, and in the control of a variety of genes that are involved in stress resistance.

Now, as the result of experiments conducted on the digestive system of C. elegans, a microscopic worm that is widely used as a research model in laboratories throughout the world, Harvard researchers have discovered that insulin inhibits a master gene regulator protein known as SKN-1, increased activity of which is known to increase lifespan. Additionally, SKN-1 is recognized as controling what is known as the Phase 2 detoxification pathway, which is a network of genes that collaborate to defend cells against oxidative damage such as that caused by free radicals and environmental toxins. As a result of these studies, a reduction in insulin signaling was found to trigger increased activity of both the FOXO and the SKN-1 proteins, thereby increasing resistance to stress and increasing longevity of life.

According to Dr. T. Keith Blackwell, a senior investigator at the Joslin Diabetes Center, associate professor of pathology at Harvard Medical School, a faculty member at the Harvard Stem Cell Institute, and the primary author of the paper, “We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies. This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize. The major implication is that we have found something new that affects lifespan and aging, and an important new effect that insulin and/or a related hormone called insulin-like growth factor-1 may have in some tissues. The implications go far beyond diabetes.”

Indeed, the work relates not only to diabetes but also to other diseases which are often secondary complications that result from diabetes, such as vascular and renal problems. Additionally, the findings also have much broader implications for health, stress, lifespan and longevity. According to Dr. Blackwell, “You can manipulate the expression of SKN-1 and the worms live longer.” Currently, Dr. Blackwell’s lab is focused on further delineation of the precise molecular mechanisms that regulate free radical resistance and aging.

Certain types of adult stem cells have already been shown to differentiate into the insulin-producing beta islet cells of the pancreas. Combined with Dr. Blackwell’s recent discovery, stem cells once again enter the realm not merely of disease treatment but also of longevity and extended lifespan.

At the annual meeting of orthopedic surgeons held in San Francisco during the week of March 3rd, doctors examined the possibility of growing new bone and possibly entire limbs from stem cells.

Currently more than 31,000 U.S. military men and women have been wounded in Iraq, 60 to 70% of whom have sustained musculoskeletal injuries. Traditionally, for blast injuries that destroy bone, military surgeons have usually applied nonorganic materials such as metal to rebuild the bone. Now, however, stem cell therapy offers a new and more effective treatment.

Such stem cell therapy would consist of the administration of stem cells either from external (allogeneic) sources, or fom naturally endogenous (autologous) stem cell sources which have been mobilized to harness the body’s innate abilities for regeneration. Dr. John Huard, Director of the Growth and Development Laboratory at the Children’s Hospital of Pittsburgh, cites animal studies in which scientists were able to regenerate bone that was identical in every way to the lost bone that it
had replaced. Dr. Scott Boden of the Emory Spine Center in Atlanta, Georgia, has been studying the possibility of growing new spinal bone and tissue in humans. Stem cells are known to naturally target those regions of the body that are in need of repair, and Dr. Boden and his colleagues have developed further ways to mobilize and control the action of stem cells within the body by attracting the stem cells with specific protein signals to specific areas that are in need of regeneration.

Dr. Scott Rodeo, co-chief of sports medicine and shoulder service at the Hospital for Special Surgery in New York, and the team physician to the Super Bowl winning team, the New York Giants, sees stem cell therapy as a preferable alternative to current surgical techniques. A major clinical problem for orthopedic surgeons is the high failure rate of “tendon-to-bone” healing in many surgical procedures, which is especially problematic in torn rotator cuffs, the surgery for which often leaves the patients in constant pain and even weaker than they were before the surgery. Infection is also a common problem associated with surgery, especially on the battlefield but also among the civilian population. In 2005 alone, approximately 18,650 people in the U.S. died of staph infections that were acquired while in a hospital. Such infections can be life-threatening because they are often highly resistant to antibiotics. According to Dr. Richard Evans, Chief of Reconstructive Surgery at the University of Arkansas, “It’s an ongoing problem that’s actually getting worse. We have new organisms that are smarter than we are.” By replacing surgery altogether with stem cell therapy, doctors would be able to eliminate such risks as infections that are secondary to surgical procedures, and other related iatrogenic illnesses.

Navy Captain Dana Covey, chairman of orthopedic surgery at the Naval Medical Center in San Diego, has been deployed to Iraq twice. He and many other doctors agree that the injuries which are occurring in Iraq present a major opportunity for medical science. According to Army Major Eric Bluman, Chief of Foot and Ankle Service at the Madigan Army Medical Center at Ft. Lewis, Washington, “There’s a huge wealth of knowledge. Normally we see blunt trauma from car accidents or bike accidents. Iraq was almost like a second fellowship for me.”

Some species, such as the salamander, are well known for their ability to regenerate entire limbs from their own, naturally occurring, endogenous stem cells. Even in many mammals, the natural, spontaneous regeneration of some tissue, on a smaller scale, is known to occur. Although further development of this science is needed before it becomes a routine therapy for humans, the regenerative power of stem cells nevertheless remains an area of intense focus and study by numerous researchers around the world.

Parkinson’s disease is a neurodegenerative disorder of the central nervous system that strikes people at the rate of approximately 1.6 per 100 persons over 65 years of age. It is estimated that over half a million people in the United States and over 4 million people worldwide suffer from Parkinson’s disease, and the global figure is expected to rise to nearly 9 million by the year 2030, according to estimates by the Parkinson’s Foundation and by the World Health Organization. Although this debilitating disease is currently considered to be irreversible and a fully effective conventional medical treatment does not exist, researchers in France have now demonstrated the power of adult stem cells to halt and reverse the progression of this disease.

Mesenchymal stem cells derived from the bone marrow of adult rats were used to treat these rats for symptoms of Parkinson’s diease. Significant improvements were measured at various intervals, with a 50% decrease in symptoms being measured as early as one week after treatment with the bone marrow-derived stem cells. Not only were behavioral symptoms restored to normal in the rats, but new neurological dopaminergic (dopamine producing) tissue was actually regenerated which dramatically corrected the characteristic absence of dopamine that typifies the brains of individuals afflicted with Parkinson’s disease.

According to the researchers of this study, treatment with adult mesenchymal stem cells “reduces behavioral effects” and “partially restores the dopaminergic markers and vesicular striatal pool of dopamine” in the rats, therefore leading the authors of the study to conclude that, “This cellular approach might be a restorative therapy in Parkinson’s disease.”

It has long been known that stem cells are found in dental pulp, not only in humans but also in other species. Now stem cells from the teeth of dogs have shown remarkable regenerative capacity.

Professor Minoru Ueda and colleagues at the Nagoya University in Japan have performed a new procedure with two sets of dogs, each set consisting of a 2-year-old adult dog and one of its 2-week-old puppies. From the dental pulp of the primary teeth of each of the puppies, stem cells were collected and differentiated into bone cells. After being mixed with plasma from the blood of the parent dogs, the new cells were then injected into holes that had been made in the jawbones of the adult dogs. One month later, in both sets of dogs, newly grown bone was found to have filled the holes, each one of which was approximately 6-tenths of an inch deep and wide.

Bone is one of the most specialized tissues of the body, in any species, and these findings not only offer an effective new therapy for the veterinary treatment of orthopedic injuries in dogs, but canine studies such as these are also translatable to potential new therapies in the treatment of orthopedic injuries in humans.

Thalassemia Major is an inherited blood disorder which is characterized at an early age by symptoms of severe anemia. Previously there has been no known cure for the disease, and until now the only known treatment has been constant blood transfusions every 4 to 6 weeks throughout life, one common complication from which is often secondary hemochromatosis, also known as iron overload, which often leads to organ failure and death. Left untreated, this particular form of Thalassemia will cause bone deformities and death within the first decade of life.

Because of this disease, the white blood cell count of this particular 4-year-old boy had dropped to zero. He was admitted to a cancer research institute in his home country of India where he was then treated with his younger sister’s cord blood, which had been banked at the Cryo Stem Cell Institute in Bangalore. The boy’s white blood cell count is now rising and he is expected to be released in 6 weeks. This is the first stem cell transplant of its type in eastern India and it offers new hope not only in the treatment of this disease but also in the treatment of other previously incurable conditions.

Dr. Hanna Mikkola and colleagues at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California at Los Angeles have announced results of the first study ever to definitively demonstrate that blood stem cells originate in the placenta.

In previous studies, researchers working with embryonic stem cells (ESCs) have tried to keep the ESCs in a perpetually self-renewing state after transplantation, but have been unable to prevent the ESCs from differentiating prematurely when transplanted into animal models. Although some success has been achieved through the use of retroviruses to manipulate the cells genetically, such procedures are generally not considered to be safe for use in humans. For this and many other reasons, ESCs have never actually been used in the treatment of human disease in human patients. Now, yet another highly preferable alternative to ESCs may be available as a human therapy.

Using a new type of mouse model, the researchers were able to identify the placenta as the origin of hematopoietic stem cells which exhibit the capacity to differentiate into all the major lineages of blood cells. The placenta can be broadly divided into two different "microenvironments", one of which comprises the large arteries in which the stem cells are manufactured, and from which the stem cells then migrate into the second environment, which is the "labyrinth" that is comprised of the "niches" in which the stem cells are "nurtured" and allowed to expand in number. These niches within the placental labyrinth are a topic of intense focus and study as researchers attempt to understand the molecular signals and cues that regulate the self-renewal of the blood stem cells without triggering differentiation. The labyrinth is also a source of many growth factors and cytokines which contribute to the action of the signaling molecules.

Building upon the work of previous scientists who were able to produce induced pluripotent stem (iPS) cells from adult skin cells, Dr. Mikkola and colleagues hope to be able to replicate the molecular signaling of the placental microenvironment in the laboratory in order to produce and regulate blood stem cells from iPS cells within this type of environment. If blood cells, differentiated from blood stem cells, could be generated from iPS cells that were taken from a person’s own skin cells, the risk of graft-versus-host disease, which is a common problem with transplantation, could be eliminated, as would the need for using embryonic stem cells.