c-Kit+ cells isolated from human fetal retinas represent a new population of retinal progenitor cells

Abstract

ABSTRACT Definitive surface markers for retinal progenitor cells (RPCs) are still lacking. Therefore, we sorted c-Kit+ and stage-specific embryonic antigen-4− (SSEA4−) retinal cells for further biological characterization. RPCs were isolated from human fetal retinas (gestational age of 12–14 weeks). c-Kit+/SSEA4− RPCs were sorted by fluorescence-activated cell sorting, and their proliferation and differentiation capabilities were evaluated by using immunocytochemistry and flow cytometry. The effectiveness and safety were assessed following injection of c-Kit+/SSEA4− cells into the subretina of Royal College of Surgeons (RCS) rats. c-Kit+ cells were found in the inner part of the fetal retina. Sorted c-Kit+/SSEA4− cells expressed retinal stem cell markers. Our results clearly demonstrate the proliferative potential of these cells. Moreover, c-Kit+/SSEA4− cells differentiated into retinal cells that expressed markers of photoreceptor cells, ganglion cells and glial cells. These cells survived for at least 3 months after transplantation into the host subretinal space. Teratomas were not observed in the c-Kit+/SSEA4−-cell group. Thus, c-Kit can be used as a surface marker for RPCs, and c-Kit+/SSEA4− RPCs exhibit the ability to self-renew and differentiate into retinal cells.