Matrix and environmental control of stem cell outcomes for tissue engineering

BIOT 94

David L. Kaplan, David.Kaplan@tufts.edu, Hyeon Joo Kim, Xiaoqin Wang, Xianyan Wang, Charu Vepari, Amanda Murphy, and Irene Georgakoudi. Department of Biomedical Engineering, Biotechnology & Bioengineering Center, Tufts University, 4 Colby Street, Medford, MA 02155
Stem cells play a vital role in functional tissue engineering due to their plasticity. In particular, human bone marrow derived mesenchymal stem cells (hMSCs) are central to many strategies in tissue engineering and regenerative medicine. In light of this role, critical issues associated with the maintenance and fate of these cells becomes important in terms of tissue specific goals. Relevant issues include the role of matrix chemistry on cellular outcomes, the role of cell-cell signaling on cell functions and the role of selective environments on the fate of the cells. The complexity of stem cell and matrix interactions, referred to as the niche, offer tremendous challenges as well as opportunities to improve both the rate and extent of tissue specific outcomes under controlled laboratory conditions. We have focused some of our efforts on these topics, including: the role of specialized or functionalized protein scaffold systems to direct stem cells toward selective outcomes, the role of stem cell–differentiated cell signaling with regard to cell recruitment, and the role of selective bioreactor environments on stem cell fate. For example, mineralized protein-composite scaffolds seeded with hMSCs and cultured in vitro under osteogenic conditions demonstrated improved osteoconductive outcomes correlated with initial content of apatite in the porous scaffolds. In a parallel study, spinner flask bioreactor systems with improved mass transport when compared to static culture, resulted in improved osteogenic outcomes from hMSCs seeded on porous protein scaffolds under osteogenic conditions. These and other results provide insight into the role of scaffold and environmental signals on osteogenic outcomes related to bone tissue engineering. These studies have been extended to new modes to control the delivery of essential cell signaling factors to gain further control of regional differentiation of the hMSCs on such scaffold systems.