UC San Diego

The ability of stem cells to differentiate and contribute to tissue repair has enormous potential to treat various debilitating diseases. However, improving the in vivo viability and function of the transplanted cells, a key determinant of translating cell-based therapies to the clinic, remains a daunting task. In this study, we developed a biomimetic polymer-based cell delivery vehicle consisting of hyaluronic acid backbone functionalized with 6-aminocaproic acid moieties (HA-6ACA) that mimics the structural and functional properties of native proteoglycans including growth factor signaling. Employing this system, we investigated the potential of such synthetic matrices to improve cell delivery and their subsequent in vivo function using skeletal muscle as a model system. Our findings show that the biomimetic material-assisted delivery of hESC-derived myogenic progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promoted survival and engraftment of transplanted cells in a dose-dependent manner. The donor cells were found to contribute to the regeneration of damaged muscle fibers and to the satellite cell compartment. The results described in this study provide a proof-of-principle that biomimetic materials not only act as a delivery vehicle but also promote in vivo survival and function of transplanted cells. Such cell delivery vehicles that are cost-effective and easy-to- synthesize offer an ideal tool to promote the outcomes of cell-based therapies