Abstract
Abstract: :
Purpose:Retinal impairment by neuronal death has been considered incurable because the central nervous system does not have a regenerative capacity. Taking advantage of the plasticity of adult stem cells, we have tested whether adult stem cells (bone marrow stem cells and injury–induced peritoneal stem cells) can be differentiated into various retinal cells both in vitro and in vivo. Peritoneal stem cells, which were recently discovered by our laboratory, can be obtained from adult human and mice in large quantity (>100X that of bone marrow stem cells) and have excellent tissue regeneration properties. Methods:Green fluorescent protein (GFP)–labeled bone marrow stem cells and peritoneal stem cells were isolated from adult transgenic mouse ubiquitously expressing GFP. Injury–recruited peritoneal stem cells were isolated from the peritonea of mice bearing polyethylene terephthalate implants for 2 days. For in vitro studies, both stem cells were incubated with ocular organ culture–conditioned media for 2 weeks. The extent and type of cell differentiation were then evaluated by immunocytochemistry. For in vivo studies, GFP–labeled stem cells were proliferated in vitro and then injected into the vitreous of eyes whose retinas had been mechanically injured using a hook needle. Two weeks after cell implantation, the mice were sacrificed and eyes sectioned. The migration and differentiation of implanted stem cells were assessed using histological technique. Results:Overall, we have discovered that novel peritoneal stem cells behave similar to bone marrow stem cells. After incubated with ocular organ culture–conditioned media, both adult stem cells differentiated into neuronal cells with cellular markers similar to those of rod bipolar, horizontal, and amacrine cells, but not retinal ganglion cells. Furthermore, shortly after transplantation, adult stem cells migrated and then differentiated into retinal neural cells in the injured retina. These transplanted GFP–positive stem cells expressed neuron–specific enolase, glial fibrillary acidic protein, vimentin and neurofilament–M. Conclusions:These results have shown that intravitreally injected adult stem cells can differentiate into cells of retinal/neuronal lineage and partially repopulate the damaged retina. Our results suggest that adult stem cells may provide a new therapeutic means to cure certain types of retinopathy.
Keywords: retina • regeneration • retinal development