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.”

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.

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.

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.

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.

New research presented at the annual meeting of the Orthopedic Research Society in San Francisco provides a more detailed elucidation of the molecular and cellular pathways by which cigarette smoke inhibits stem cell activity.

Bone healing is a two-step process which begins when stem cells differentiate into cartilage and ends when the cartilage has matured into bone. Cigarette smoking has been known to delay skeletal healing after fractures and other injuries by as much as 60%, thereby increasing the risk of further re-injury and chronic disability or pain. In 2005, researchers at the University of Rochester Medical Center in New York identified nicotine as a chemical which interferes with bone growth by altering gene expression. Now the same researchers have identified another chemical in cigarette smoke which also inhibits bone healing, namely, hydrocarbon benzo[a]pyrene (BaP). This polyaromatic hydrocarbon has now been found to prevent the stem cells from reaching the first step in the process, so that they are unable even to begin differentiating into cartilage. Through PCR – polymerase chain reaction, a technique which measures the level of gene expression – the scientists were able to use a mouse model in which they measured genetic changes that were caused by exposure to BaP. Gene expression is the process by which proteins are manufactured through the execution of instructions that are encoded within the genes. Many factors may influence gene expression, one of which is a transcription factor known as the "sex determining region Y-box 9" (SOX-9), which is required for the differentiation of cartilage from stem cells. In this study, the scientists were able to demonstrate by PCR that BaP interferes with SOX-9 expression in mesenchymal stem cells by blocking the conversion of the cells into cartilage and also by reducing levels of type II collagen gene expression. Previous studies have demonstrated that stem cells which are involved in cartilage formation contain proteins known as aryl hydrocarbon receptors (AhR) and that are known to react with BaP. When BaP binds with these receptors, SOX-9 activity is suppressed which results in a reduction both in the number of stem cells that differentiate into cartilage and in the amount of collagen that is produced. The receptors are believed to be involved in the cellular signaling pathways that are responsible for the metabolism of toxins. Staining experiments have also demonstrated that BaP inhibits the deposition of collagen nodules which are indicative of differentiated cartilage cells in vitro.

According to Michael Zuscik, Ph.D., associate professor in the Department of Orthopedics and Rehabilitation at the University of Rochester Medical Center, "Smoking reduces the rate at which the two sides of a fracture come together. We believe this new research will establish for the first time the mechanisms by which polyaromatic hydrocarbons interfere with the healing process."