Bridget M Deasy

	Department of Orthopedic Surgery	LIVE CELL IMAGING LAB
	Stem Cell Research Center	McGowan Institute for Regenerative Medicine

Funding Support

Live Cell Imaging in Stem Cell Characterization. Excitement in the field of regenerative medicine is fueled by the potential of stem cells to give rise to multiple cell fates and repair damaged tissue. Yet the phenotypes which prospectively identify potent stem cell populations are not well understood. We believe this is because the structure and dynamics of subpopulations, within the stem cell population, are not well characterized. Several different subpopulations - including quiescent, mitotic, and transiently amplifying cells - contribute to proliferative and molecular heterogeneity. Ultimately, this heterogeneity complicates the identification of the subpopulation that may be most responsible for the beneficial activities of stem cells (i.e. self-renewal and multipotency). Live cell imaging (LCI) is a tool uniquely able to capture these dynamics. LCI provides live viewing of the behavior of a stem cell population in culture and allows us to obtain numerous real-time measurements at the single cell level. The result is a detailed behavioral phenotype of the stem cell population which can be linked to in vivo outcome measures.
	Expandability and cell fate are controlled via asymmetric fate and divisions
Cell lineage histories provide unique data on cell fate
Human umbilical cord cells for musculoskeletal tissue engineering. In these projects we study human stem cells from umbilical cord (UC) for their potential in cell therapy for musculoskeletal tissue regeneration. Several characteristics of these cells make them attractive for cell therapeutics. First, the readily available source of human umbilical cord tissue and the current clinical success of cord blood transplantation for hematological disorders suggest an expedited route for translation to other therapies. Second, as an allogeneic transplantation, UC cells are more histocompatible than adult-derived cells, require fewer HLA matches and report reduced graft-versus-host disease. Third, there is a reduced likelihood of infectious disease contamination. Recent reports have described the multipotentiality beyond the hematopoietic lineage for UC-derived cells, and include studies of cardiac, liver and spinal cord disorders. Yet there are many unexplored aspects, particularly for musculoskeletal tissues. Here, we explore the origin and mesodermal lineage differentiation of stem cells derived from the umbilical cord, and evaluate the expansion potential of the human stem cell populations in terms of cell numbers and in terms of the stability of the stem cell phenotype.
	The umbilical cord contains stem cells which can be used for musculoskeletal tissue repair
Human umbilical cord after full-term, healthy delivery
Sex differences in muscle stem cells One disease for which stem cell therapy holds promise is Duchenne muscular dystrophy (DMD). DMD is a muscle disease characterized by severe and progressive muscle weakness due to the lack of dystrophin protein expression at the sarcolemma of muscle fibers. Onset occurs early in childhood (between 2 and 6 years of age), and survival beyond 30 years of age is rare. The lack of dystrophin in the muscle disrupts the structural connection between the cytoskeleton and the extracellular matrix, resulting in muscle fiber necrosis and weakness. Effective treatment of DMD will require replacing the missing dystrophin protein. Because of the natural tendency of muscle progenitor cells to fuse with existing or newly forming muscle fiber cells, cell transplantation-based approaches to DMD treatment are very promising. Indeed, research has shown that allogeneic muscle progenitor cells (such as myoblasts) can fuse with host cells after transplantation into injured or diseased tissue in which the host cells are undergoing regeneration (e.g., in dystrophic tissue). Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin expression, the use of less-committed stem cells can improve the efficiency of this approach. Specifically, the use of mouse muscle-derived stem cells (mMDSCs), which have unique properties, has enhanced the success of cell transplantation in mdx mice, which model DMD.
	Female muscle stem cells may have increased muscle regeneration due to intrinsic differences in stress response mechanisms
Male and female stem cells exhibit differences in their participation in muscle repair

Copyright 2009 Deasy, BM
University of Pittsburgh

Live Cell Imaging Lab
5106 Rangos Research Center
Stem Cell Research Center
University of Pittsburgh
Pittsburgh, Pennsylvania 15213