Defining BMP-Mediated Epigenetic Regulation of Induced Pluripotent Stem Cells for Bone Regeneration
As our population continues to age, a concomitant increase in the incidence of diseases involving the musculoskeletal system is expected. Current approaches to address skeletal injuries and defects are limited, and thus a pressing need exists for the development of alternative cell-based strategies for bone reconstruction. Stem cells represent a powerful tool with the potential to treat a wide range of diseases. Ultimate clinical application, however, has been hampered by the limited ability to effectively guide these cells in a safe manner toward desired targets. However, we believe that the way genetic material is regulated may be exploited to coax stem cells toward bone formation. We will test this theory by first determining all the changes that occur in these cells in response to compounds known to enhance the generation of bone. We will then look to mimic these changes and evaluate the strength of this approach to guide our stem cells toward bone. Finally, we will employ a mouse model to investigate the both the safety and efficacy of our approach to promote human stem cell-mediated bone regeneration in an animal engineered to not reject human cells. Together, these studies will lead to the development of a powerful therapeutic strategy to improve skeletal regeneration in our aging population.
The most significant social, political, and economic problem we face in California and in the United States is our aging population. Nearly 20% of the population in this state is presently 55 years or older. Worldwide, within the next five years, the WHO reports that the number of people over age 65 will outnumber those under 5. As our age demographics continue to shift, a concomitant increase in incidence of diseases involving the musculoskeletal system is expected. This stems from a multitude of etiologies including post-surgical, post-traumatic, and degenerative conditions. In 2007 alone, the biomedical burden attributed to diseases of the musculoskeletal system was reported to exceed 26 billion dollars, and this figure has continued to increase in more recent years at an estimated rate of 8.5% annually. Treatment of bone related problems, however, is not limited to the elderly, as children born with congenital anomalies also frequently require skeletal reconstruction. In light of these facts, better approaches to the treatment of skeletal defects and deficiencies must be developed. Our proposal addresses this need by developing a strategy to harness the regenerative potential of stem cells in a safe and effective manner. As studies have shown the ability for stem cells to form bone, we explore this potential with the ultimate goal of actualizing a powerful therapeutic strategy to treat skeletal deficiencies for citizens of California and beyond.