A critical bottleneck in translating regenerative medicine to the clinic is the efficient delivery and engraftment of transplanted stem cells. While direct injection is a minimally invasive method for stem cell delivery, unfortunately it commonly results in massive cell death. Several studies suggest that delivery within a carrier gel may enhance stem cell viability; however, the majority of these studies have used naturally derived materials that are not suitable for clinical translation.
During the period of this award, we developed a family of injectable, cell-delivery materials that are fully defined for FDA-approval in clinical studies. To provide focus for our studies, we specifically sought to improve the delivery of human induced-pluripotent stem cell-derived neural progenitors (hiPSC-NPs) for the treatment of acute spinal cord injury (SCI). In the first two years, we designed, expressed, and mechanically characterized different variants of our injectable hydrogel system (named SHIELD for Shear-thinning Hydrogels for Injectable Encapsulation and Long-term Delivery) with varying biochemical cell-adhesive ligands and degradation rates, with the goal of improving long-term hiPSC-NP cell survival and function. In the last year of this award, we evaluated the ability of SHIELD to promote cell viability and engraftment, tissue regeneration, and functional improvement in a rat model of acute SCI. We demonstrate that delivering hiPSC-NPs within SHIELD significantly improves the recovery of forelimb function in animals. Initial immunohistological analysis suggests that this is in part due to the increased delivery of hiPSC-NPs in SHIELD compared to saline.
We will continue to evaluate the ability of SHIELD to enhance transplanted stem cell viability, and hence improve clinical outcome of diseases, using animal models for chronic SCI as well as animal models for other disease indications.