Improving the therapeutic functionality of neural progenitor cells by encapsulation with chondroitin-4-sulfate-a hydrogel

Abstract

Stroke is a growing cause of morbidity and a significant cause of mortality in the United States. Currently, no therapies can promote recovery of neuronal networks lost to cerebral infarction. Tissue engineering strategies such as cellular therapy may be able to enhance functional regeneration of brain tissue. Neural progenitor cells (NPCs) are at the forefront of preclinical studies for regenerative stroke therapies. NPCs can differentiate into and replace neurons and promote endogenous recovery mechanisms. The stroke core region is the ideal location for replacement of neural tissue since it is in situ, and following degradation, develops into a potential space for targeting injections. However, the compromised cortical perfusion and degradation of the extracellular matrix following ischemia create an inhospitable environment resistant to cellular therapy. Overcoming these limitations are critical for clinical translation. In our studies, we test whether encapsulation of NPCs in a chondroitin-4-sulfate-A (CS-A) hydrogel enhances their ability to repair the injured brain following stroke in mice. We show that CS-A encapsulated NPCs improve vascular regeneration at multiple levels to increase cerebral blood flow. These outcomes are likely mediated by enhanced paracrine signaling effects and regenerative immunomodulation. Further research and additional strategies are necessary to overcome the shortcomings of CS-A encapsulated NPC treatment. In summary, extending the therapeutic potential of NPCs using angiogenic biomaterials such as CS-A may be a viable solution to overcoming limitations for regenerative cellular therapy in ischemic stroke.