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

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.