Abstract
Abstract: :
Purpose: To determine if exogenous hematopoietic stem cells (HSC) injected intravenously (iv) can home to the subretinal space in a murine model of retinal pigment epithelium (RPE) loss. Methods: GFP+–cells of bone marrow origin were used in a sodium iodate (NaIO3) model of RPE loss in the C57BL/6 mouse. Mice were injected iv with 50 mg/kg NaIO3 followed by the iv injection of either bone marrow cells (BMC, 15x106), HSC (15,000), HSC (15,000) + facilitating cells (FC, 30,000 ) or mononuclear cells (MNC) from Flt3 ligand (FL)–mobilized peripheral blood (PB, 10x106) on day 3. The mice were sacrificed on day 10 (1 week post–injection) or day 17 (2 weeks post–injection). Whole eye flat mounts were prepared and examined for GFP+ cells under a laser scanning microscope (argon laser). Immunocytochemical analysis was also performed on several tissues (eyes, lung, spleen, kidney, liver, heart) for CD–45 or GFP. Results: With 50µg/ml of NaIO3 patchy RPE damage was observed starting on day 3. At both one and two weeks after the iv injection of stem cells, GFP+ and CD45+ cells were observed in the subretinal space at the sites of RPE loss. No GFP+ or CD45+ cells could be found in the subretinal space in control animals without NaIO3 injection. No statistically significant difference could be found in the number of stem cells in the subretinal space if the time of iv injection varied. The combination of HSC + FC resulted in the highest number of stem cells in the subretinal space at two weeks. Conclusions: Exogenous HSC from a syngeneic murine donor are capable of homing to the subretinal space in a murine model of RPE cell loss. The combination of HSC with FC resulted in the largest number of stem cells in the subretinal space. It is not known whether these cells are capable of replacing the damaged RPE.
Keywords: retinal pigment epithelium • transplantation • retinal degenerations: cell biology