Neurodegenerative diseases and central nervous system injuries cause life-changing motor and sensory deficits as a result of severe loss of neurons in the central nervous system. Cell replacement therapies using patient-derived cells reprogrammed into neurons have the potential to restore normal function, however, typical cell transplantation involves forcefully detaching cells from growth surfaces and result in limited transplanted cell survival, functionality, and engraftment. In this collaboration between Professor Moghe’s lab and the NJCBM, an optimized molecular composite of a tyrosine-derived polycarbonate was used to create three-dimensional polymeric scaffolds with tunable microscale topography. The maturation of reprogrammed neuronal populations was enhanced on some scaffold geometries, and these cell populations were observed to have significantly fewer dividing and potentially tumorigenic cells. Scaffold-supported reprogrammed neuronal cell population successfully engrafted into hippocampal brain slices, with a 3.5-fold improvement in neurite outgrowth and increased action potential firing relative to dissociated single cells. Scaffolds also improved the survival rate of neurons transplanted into mouse brain 38-fold. Overall, these studies demonstrate that the development of optimized polymeric scaffolds was a critical component of the successful cell transplantation reported here. Cell-scaffold interactions should be a major consideration guiding the design of scaffolds in transplanting neuronal cell populations.
This research was just published in Nature Communications, and featured here.