Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment.

The ability of human embryonic stem cells (hESCs) and their derivatives 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. Here, we develop a hybrid biomaterial consisting of hyaluronic acid (HA) grafted with 6-aminocaproic acid moieties (HA-6ACA) 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 promotes 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 (muscle specific stem cells) compartment. Such biomimetic cell delivery vehicles that are cost-effective and easy-to-synthesize could play a key role in improving the outcomes of other stem cell-based therapies.