Thermoswitching microgel carriers improve neuronal cell growth and cell release for cell transplantation

Successful cell replacement therapy in the central nervous system (CNS) depends on both the transplanted cell type and the cell delivery method. It was established that differentiated neurons are the most desirable cell source; however, they are highly sensitive to dissociation shear; removing them from the growth surface inflicts serious damage, rendering them less viable for transplantation. Pilot experiments using glass colloids as injectable cell carriers for cell transplantation in the adult rat hippocampus have greatly improved neuron survival and long-term neuron integration. However, these early studies have highlighted glass particle shortcomings. They are uncompressible, and, thus, only a small number of beads can be injected, limiting the transplanted cell number. Moreover, they remain permanently in the brain. To improve colloidal carriers properties for cell transplantation and establish a basis for the next generation of cell delivery supports, we have designed a broadly applicable engineering strategy to enable neuronal cell growth on and release from hydrogel particles before transplantation. Here, we describe poly(N-isopropylacrylamide) (pNIPAM) particle preparation, and we demonstrate that these hydrogel particles both facilitate manipulation of neurons and enable the increase in the number of viable transplanted cells in the young adult rat hippocampus. The absence of long-term cell association to beads suggested that pNIPAM thermoswitching properties enable the separation of cells from the beads during injection, which minimizes the number of injected carriers. Contrary to observations with glass carriers, no particle clumping was observed at the injection site, which indicates minimal risk of long-term inflammatory responses. Taken together, the properties of hydrogel particles make them a promising micro-carrier to improve neuronal cell transplantation.