Enabling cell-based therapy of spinal cord injury through injectable hydrogels

Spinal cord injury (SCI) causes permanent damage to about 12,000 new patients in the US each year, primarily young adults. A common result of SCI is paralysis, and unfortunately, less than 1% of SCI patients have full neurological recovery by the time of hospital discharge. To develop a regenerative therapy for SCI, many researchers have been focusing on the stem cell transplantation therapies that have resulted in partial regeneration in preclinical animal models. However, the delivery of a sufficient number of stem cells remains a difficult and unmet challenge. Only about 5% of cells survive after injection, partly due to mechanical damage. To address this problem, we have designed a very soft hydrogel that can be injected together with cells to protect cells and enhance cell survival. Following injection, we hypothesize that a hydrogel mimicking the native tissue stiffness could best support cells towards tissue regeneration. Therefore, I propose a next-generation family of hydrogels that are soft during injection to protect cells and can be tuned to have a range of stiffnesses after injection to mimic native nerve tissue. I will customize these hydrogels to deliver human induced-pluripotent stem cell-derived neural progenitors (hiPSC-NPs), which have a great potential for cell-based therapy of SCI. Using this hydrogel-based strategy, I aim to enhance hiPSC-NP survival after injection, promote neurite extension, and improve functional recovery in a rat SCI model..