Stem Cell Plasticity
Adult stem cells exist as a reservoir for tissue repair during homeostasis. They have a remarkable capacity for self-renewal in an undifferentiated state and can differentiate to replace damaged cells in tissue. It may be possible to harness the unique properties of stem cells to cure disease, regenerate tissue, repair traumatized tissue and reverse the degenerative effects of aging.
Recent reports indicate that adult stem cells possess a much wider differentiation potential than was previously thought. While it is generally recognized that adult stem cells differentiate into mature cells within the embryonic germ layer of their origin, there is growing evidence that they exhibit plasticity across this boundary. Plasticity will greatly expand the therapeutic applications of adult stem cells to repair a variety of damaged tissues. Our research group is investigating factors that influence the plasticity of human bone marrow stromal cells.
Stem-Cell Enrichment
One of the challenges to realizing the therapeutic potential of stem cells is their scarcity in adult tissue. To collect the quantity of cells required for clinical procedures, stem cells are subject to ex vivo amplification. Although adult stem cells can repair tissue in vivo throughout an entire lifetime, they do not proliferate and differentiate as effectively ex vivo. Preserving the regenerative capacity of stem cells during amplification is essential to the development of effective stem cell therapies and is the subject of research in our laboratory.
Clinical applications of human bone marrow stromal cells are limited by rapid depletion of progenitors from culture during ex vivo amplification. As a consequence, improved amplification methods that enrich progenitor content are required for marrow stromal cells to be a feasible cell source for stem cell therapies. Our research group utilizes an integrative experimental and computational approach to achieve a mechanistic understanding of progenitor enrichment that will facilitate the rational design of amplification strategies.
Tissue Assembly
A new era in tissue engineering is emerging, one which interfaces with computer science. This trend parallels the integration of computational analysis into the biological sciences as a whole. Computation has dramatically changed the degree of complexity in research and yielded significant insight into living systems. To date milestones in tissue engineering have been achieved largely through empirical investigation. Mathematical models have the potential to significantly influence future developments in this field given the intrinsic complexity of its products. Our research group has developed a computational model that predicts the kinetics of tissue self-assembly. The representative system for this work is spheroids of human prostate cancer cells that have application to high-throughput and patient-specific drug testing.