Transplantation of brain cells assembled around a programmable synthetic microenvironment

Cell therapy is a promising method for treatment of hematopoietic disorders , neurodegenerative diseases, diabetes, and tissue loss due to trauma. Some of the major barriers to cell therapy have been partially addressed, inclu ding identification of cell populations, in vitro cell proliferation, and s trategies for immunosuppression. An unsolved problem is recapitulation of t he unique combinations of matrix, growth factor, and cell adhesion cues tha t distinguish each stem cell microenvironment, and that are critically impo rtant for control of progenitor cell differentiation and histogenesis. Here we describe an approach in which cells, synthetic matrix elements, and con trolled-release technology are assembled and programmed, before transplanta tion, to mimic the chemical and physical microenvironment of developing tis sue. We demonstrate this approach in animals using a transplantation system that allows control of fetal brain cell survival and differentiation by pr eassembly of neo-tissues containing cells and nerve growth factor (NGF)-rel easing synthetic particles.