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EM Frenzel, M Reyes, CM Verfaillie, KR Zahs, ER Steuer; Transplantation of Adult Bone Marrow-Derived Progenitor Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3693.
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Purpose: Photoreceptor cells in the adult mammalian retina do not regenerate, and no effective treatment for visual impairments due to photoreceptor cell loss exists. We are examining the potential of multipotent adult progenitor cells (MAPCs) derived from bone marrow to repair damaged retina, either by differentiating into photoreceptor cells or by exerting trophic influences on host cells. MAPCs express markers for neurons, astrocytes, and oligodendrocytes when grown in fibroblast growth factor 2. Other investigators have reported the migration and integration of hippocampal progenitor cells into dystrophic or injured retina following transplantation, yet, thus far, not the expression by the cells of markers for photoreceptor cells (Nishida et al, IOVS2000; Young et al, Mol Cell Neurosci2000). As an initial effort, we investigated whether MAPCs could survive and migrate into the retina after transplantation into the subretinal space of non-diseased rabbit eyes. Method: Cells negative for CD45 and Glycophorin A were isolated from adult human bone marrow, grown on fibronectin-coated plates, and transduced with eGFP containing retroviral vector. In one eye of Dutch belted rabbits, 2 x 105 cells were injected through a 30-gauge cannula into the subretinal space inferior to the nasal wing. Subsequently, rabbits were immunosuppressed with cyclosporin A. At specific times after transplantation, rabbits were perfused with paraformaldehyde, and eyes were enucleated, post-fixed for 1-2 hours, frozen in OCT and cryosectioned. Sections were stained with a nuclear marker to identify retinal layers. MAPCs (eGFP positive cells) were localized within the sections using fluorescence microscopy. Results: Numerous green fluorescent cells were observed in the subretinal space and within the retina in cryosections of rabbit eyes 4 to 23 days after transplant. At the earlier time points, the cells were localized to the subretinal space, outer edge of the neural retina and retinal pigment epithelial cell layer. By 14 to 23 days after transplant, the cells were seen primarily in the outer nuclear layer of the retina. The eGFP+ cells were round to fusiform in shape. Conclusion: Multipotent adult progenitor cells derived from human bone marrow were able to survive when transplanted into the subretinal space of rabbit eyes. The localization of MAPCs within the outer retina suggests the migration of cells out of the subretinal space. To determine whether the transplanted cells have differentiated, antibodies to neuronal markers and to specific retinal cell markers will be used in additional studies.
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