Engineered Tools to Advance Cell Transplantation in the Nervous System Towards a Clinical Reality

Abstract Purpose of the Review The goal of this review is to highlight engineered tools for overcoming challenges in cell survival and engraftment for tissue regeneration and mitigation of neuropathic pain following cell transplantation for neural applications. Recent Findings There is a growing body of evidence supporting the safety of cell transplantation for the treatment of injuries to the brain, spinal cord, and peripheral nerves. However, the efficacy of these cell therapies is inconclusive, and the path forward remains unclear due to a lack of evidence of transplant survival and engraftment. Engineered biomaterials offer promising pre-clinical evidence of enhanced survival and engraftment of cells transplanted within the nervous system. Biomaterials have been used alone or in combination with drug and gene delivery to direct cell transplant outcomes and represent a future direction for clinical evaluation given pre-clinical survival rates that may eliminate reliance on systemic immunosuppression. Summary Biomaterial approaches under pre-clinical evaluation can support cell survival, localize cells in the injured tissue where they are needed, and enable tissue engraftment, yet have not advanced towards the clinic. Existing biomaterials provide passive support of survival during delivery and/or place a premium on supporting cell engraftment, but active remediation of tissue-local inflammation that inhibits transplant survival and leads to neuropathic pain has seen very little advancement in recent years. Combinatorial approaches capable of addressing challenges in both survival and engraftment of cell transplants in the nervous system represent an area for significant growth in the coming years.