This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports work to develop effective stem cell technologies to repair damaged bone by gaining insight into the heterogeneity of bone marrow-derived, human mesenchymal stem cells (MSCs) at the cellular and molecular levels. MSCs are a promising source of adult stem cells for bone formation (osteogenesis) and are composed of a mixture of highly regenerative and more lineage-committed cells. At present, the underlying heterogeneity of MSCs is generally not considered in the development of cellular bone therapies with implanted MSCs and molecular therapies to augment bone formation by MSCs. This project challenges the current approach by suggesting that the extent of osteogenesis in a heterogeneous MSC culture is a function of its cellular composition and molecular crosstalk among the cell populations. At the cellular level, an objective of this project is to develop a method to enrich highly regenerative MSCs to enable consistent and rapid production of effective MSC therapies to treat bone defects and other disorders. At the molecular level, computational modeling will be employed to resolve a network of Wnt pathways essential to bone formation and, in so doing, identify new pharmacological agents to enhance the effectiveness of MSCs to repair damaged bone. These research objectives are integrated with educational objectives to provide interdisciplinary training for graduate students through a unique bioengineering curriculum and collaborative research; interest high school students in science, technology, engineering and math through outreach programs sponsored by Tulane University; include underrepresented groups in these endeavors, and broadly disseminate project results to students, scholars and the public at large.
