Hope, Hype Often Cloud Stem Cell Advances, Particularly in Nonembryonic Research

Researcher

Dr. Gerrit Bouma

The phrase "stem cells" triggers a veritable avalanche of reactions – controversial, groundbreaking, hype, miracle cures, societal division, political football, biomedical advances, and, finally, hope for the incurably ill. For all that has been written and debated, one thing is certain. A lack of clarity around stem cells fuels a debate that often hides scientific advances being made in less controversial adult stem cells and induced pluripotent stem cells.

The use of stem cells as medical therapy has been around for more than five decades. Bone marrow transplants, which concentrate either a patient's own or donated bone marrow stem cells, are used most commonly to treat leukemia, Hodgkin's disease, multiple myeloma, and immunodeficiency disorders. At the College of Veterinary Medicine and Biomedical Sciences, researchers are pursuing investigations into the role of stem cells in early pregnancy and connections to preeclampsia; how bone marrow stem cells may enhance healing in horses with tendon and joint injuries; stem cells and kidney disease in cats; and much more.

"The term stem cell is quite broad and covers many different types of cells," said Dr. David Frisbie, Associate Professor in the Department of Clinical Sciences and a faculty member with the Orthopaedic Research Center. "But two common features of all stem cells are that they can self-replicate and, with correct signaling, can differentiate to any type of cell in the body."

Types of Stem Cells

Embryonic stem cells are primitive (undifferentiated) cells derived from a five-day preimplantation embryo that are capable of dividing without differentiating for a prolonged period in culture. From embryonic stem cells come all of the body's 212 cell types.

Somatic (adult) stem cells are undifferentiated cells found in smaller numbers in many organs and tissues with a limited capacity for both self-renewal (in the laboratory) and differentiation. Such cells vary in their differentiation capacity, but are usually limited to the cell types in the organ of origin, such as kidneys, liver and pancreas. Some of these cells are prolific, like those found in bone marrow, while others rarely divide, like those found in the pancreas.

Induced pluripotent stem cells are somatic cells that have been manipulated to enter an embryonic stem cell–like state by being forced to express factors important for maintaining the "stemness" of embryonic stem cells. Mouse iPSCs were first reported in 2006 and human iPSCs were first reported in late 2007. Researchers are actively comparing iPSCs and embryonic stem cells to identify important similarities and differences.

Fields of Study

Many scientists study embryonic stem cells to better understand how normal human development takes place, as well as to understand the normal and abnormal functioning of stem cells. At Colorado State University, Drs. Gerrit Bouma and Quinton Winger, both Assistant Professors in the Department of Biomedical Sciences, are investigating the role of sheep stem cells in embryonic placental implantation, and correlations between abnormal implantation and the later development of preeclampsia in the mother. Stem cells are not only studied to understand normal biology, but also to understand the biology of disease.

The use of autologous (self) stem cell transplantation, using somatic stem cells, is an active area of research looking particularly at how this technique can be used as adjuvant therapy to enhance healing and recovery from treatments such as limb-sparing surgeries in cancer patients, bone grafts, skin grafts, and tendon and ligament injuries as well as to augment injuries treated with arthroscopy. Dr. Frisbie's team has shown increasing rates of return to work for horses treated with bone marrow stem cells following arthroscopy as compared to those horses with similar injury that did not receive the additional therapy. Kidney disease in cats is also an active area of investigation for researchers at CSU, looking at the potential of somatic stem cell transplants to slow the rate of disease progression in patients.

Drug discovery is another important area of research. Once diseases are carefully modeled, researchers can study disease processes in controlled environments where drug therapies can be designed, tailored, and studied for effectiveness on the exact cells they are designed to treat.

Most controversial is research into the potential use of embryonic stem cells for treatment of a multitude of diseases, including Parkinson's disease, heart disease, Alzheimer's, multiple sclerosis, and others. This is known as regenerative medicine, using stem cells to regenerate or replace damaged tissues and organs. Research under way today uses existing cell lines. Uncertainty surrounds embryonic stem cell research programs in the United States due to court challenges and changing governmental regulations, particularly regarding federal funding of these research endeavors. Other concerns include the efficacy of embryonic stem cells because of possible health risks, ethical issues, and costs.

"Even if science can move forward with these studies, there are some pretty big challenges to the use of embryonic stem cells in medical practice," said Dr. Frisbie. "For our research, we are focused on adult stem cells, particularly those found in the bone marrow."

The science and medicine of stem cells is further complicated in the public's mind by health clinics that proffer dubious claims of cure and longevity without rigorous scientific analysis of their treatment protocols. Vulnerable Americans looking for cures to devastating illnesses are often lured by promises of health and wellness. Stem cell tourism is an exploitation of the promise of stem cells offered outside of the United States because rigorous standards would not allow such treatments here, notes Dr. Jeanne Loring, Director for Regenerative Medicine at Scripps Research Institute.

"When looking at stem cell therapy what we are interested in is what works best," said Dr. Frisbee. "With 200-plus different cells types, we want stem cells that can turn into anything. Because rejection is a concern, we want stem cells that are genetically identical to the patient. Because of ethical concerns, we want stem cells that are widely acceptable to the public for use. Adult somatic stem cells and the recent discovery of induced pluripotent stem cells address many of these considerations.

There are a lot of hurdles to developing stem cell therapies, but when you look at the progress that has occurred in the short time since the first human stem cell was isolated in 1998, I have no doubt that we will move forward."