Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1α

The chemokine SDF-la plays a critical role in mediating stem cell response to injury and disease and has specifically been shown to mobilize neural progenitor/stem cells (NPSCs) towards sites of neural injury. Current neural transplant paradigms within the brain suffer from low rates of retention and engraftment after injury. Therefore, increasing transplant sensitivity to injury-induced SDF-1 alpha represents a method for increasing neural transplant efficacy. Previously, we have reported on a hyaluronic acid-laminin based hydrogel (HA-Lm gel) that increases NPSC expression of SDF-1 alpha receptor, CXCR4, and subsequently, NPSC chemotactic migration towards a source of SDF-1 alpha in vitro. The study presented here investigates the capacity of the HA-Lm gel to promote NPSC response to exogenous SDF-1 alpha in vivo. We observed the HA-Lm gel to significantly increase NPSC transplant retention and migration in response to SDF-1 alpha in a manner critically dependent on signaling via the SDF-1 alpha-CXCR4 axis. This work lays the foundation for development of a more effective cell therapy for neural injury, but also has broader implications in the fields of tissue engineering and regenerative medicine given the essential roles of SDF-1 alpha across injury and disease states. (C) 2016 Elsevier B.V. All rights reserved.