Scaffolds for Neural Stem Cell Tissue Engineering
Stroke is a leading cause of long-term disability and there is a high unmet clinical need for therapies that allow patients to recover lost function. Neural stem cells are good candidates for treating stroke since they can self-renew, secrete beneficial trophic factors, and differentiate into mature central nervous system (CNS) cells; however, most cells die after transplantation. In this work, injectable biomaterials were optimized as transplantation scaffolds for human neural stem/progenitor cells (hNSPCs) with the goal of improving transplanted cell survival. Biomaterials including fibrin, hyaluronic acid, laminin, collagen, and reflectin were combined and tailored to promote hNSPC function. Parameters for scaffold optimization included sensitivity to mechanical stimuli since we discovered that NSPC differentiation can be regulated by static stretch when cells adhere to specific substrate materials and mechanosensing in these cells is regulated by the stretch-activated ion channel Piezo1. Further characteristics of the scaffold included material properties, polymerization and degradation kinetics, ability to support vascularization and hNSPC function, and injectability into naïve and damaged CNS tissue. A novel salmon fibrin-hyaluronic acid-laminin combination scaffold for hNSPC tissue engineering was developed in vitro, and this work marked the first report for the use of both human neural and vascular cells within a biomaterial to promote vascularization. This developed transplant construct was used in vivo in a preclinical transient middle cerebral artery occlusion (tMCAO) stroke model in rats as a potential therapeutic.