Dynamic Culture Systems with Tissue-specific Microcarriers for Human Adipose-derived Stem Cell Expansion and Delivery

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Adipose tissue (fat) is a rich source of adult stem cells, termed adipose-derived stem cells (ASCs), which hold great promise for a range of applications in tissue engineering and regenerative medicine. ASCs can be stimulated to proliferate and differentiate into more specialized cell types, including mature fat, bone, muscle, and cartilage cells, amongst other lineages. However, the cell culture environment dramatically impacts the ASC response. ASC proliferation rates decline and the cells rapidly lose their multilineage differentiation capacity when expanded using traditional cell culture methods on tissue culture polystyrene. As clinical applications may require purified stem cell populations in excess of 1 billion cells, there is a significant need for new cost-effective cell culture technologies that enable the procurement of large, well-characterized ASC populations, with preserved stem cell potential, from small tissue biopsies. This research program focuses on the development of bioreactor strategies for human ASC expansion and multilineage (bone, cartilage, fat) differentiation. To closely replicate the composition of the native extracellular environment of the ASCs, methods for the fabrication of tissue-specific microcarriers derived from the natural extracellular matrix (ECM) proteins that are found in human fat will be established using electro-spraying. Dynamic culture systems for ASC proliferation and differentiation on these microcarriers will be developed and optimized. The effects of oxygen tension and co-culturing with mature cell populations will be systematically explored to tune the cell response. Cell and molecular biology characterization tools, including analyses of gene and protein expression, will be employed to develop an in-depth understanding of the impact of the cell culture microenvironment on the ASCs. This program will provide invaluable training opportunities for HQP in the multidisciplinary areas of stem cells, biomaterials, and tissue engineering, and the trainees will develop extensive skills that integrate the fields of engineering and biology. Overall, this work will advance the clinical translation of ASC-based therapies in applications including reconstructive, orthopedic, cardiovascular, and neurological surgery.