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Y. Li, P. Atmaca–Sonmez, C. Schanie, S.T. Ildstad, H.J. Kaplan, V. Enzmann; Endogenous Bone Marrow–Derived Stem Cells May Be Able to Replace Damaged Retinal Pigment Epithelium in a Murine Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1768.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether bone marrow–derived stem cells (BMSC), after mobilization, will home to the site of sodium iodate–induced retinal pigment epithelium (RPE) damage in the subretinal space and express the markers of RPE lineage.
RPE damage was created by a single i.v. injection of sodium iodate (NaIO3, 35 mg/kg) into C57BL/6 mice or green fluorescence protein (GFP) chimeric mice. BMSC were mobilized into the peripheral circulation by intraperitoneal injection of granulocyte colony stimulating factor (G–CSF; 7.5 µg days 1–6) and/or flt3 ligand (FL; 10 µg days 1–10). Fluorescence–activated cell sorter (FACS) was used to count the number of BMSC in the peripheral blood. Immunocytochemistry using antibodies against GFP, stem cell– and RPE–specific markers was applied to visualize homing and the expression of RPE markers by BMSC in the subretinal space.
The combination of G–CSF and FL had the maximum effect on BMSC mobilization into the peripheral blood in the NaIO3 model with a 77–fold increase compared to controls. BMSC, characterized as stem cell antigen–1 (Sca–1) – or c–kit–positive cells, were found in the damaged subretinal space. Furthermore, BMSC double–labeled for GFP and the RPE markers RPE65 or microphthalmia–inducing transcription factor (MITF) were also found in the subretinal space. These cells formed a monolayer on Bruch’s membrane in sites of RPE damage at 4 and 8 weeks.
Mobilized BMSC can home to sites of RPE damage and express markers of RPE lineage. The potential of these cells as therapy in models of age–related macular degeneration is being explored.
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