Harris Jeffrey R, Brown Gary A J, Jorgensen Marda, Kaushal Shalesh, Ellis E Ann, Grant Maria B, Scott Edward W
Program in Stem Cell Biology, University of Florida, Gainesville, Florida 32610, USA.
Invest Ophthalmol Vis Sci. 2006 May;47(5):2108-13. doi: 10.1167/iovs.05-0928.
To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs) can home to and regenerate the retinal pigment epithelium (RPE) after induced injury.
Enriched HSCs/HPCs from green fluorescent protein (gfp) transgenic mice were transplanted into irradiated recipient mice to track bone marrow-derived cells. Physical damage was induced by breaching Bruch's membrane and inducing vascular endothelial growth factor A (VEGFa) expression to promote neovascularization. RPE damage was also induced by sodium iodate injection (40 mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression, the presence of the Y chromosome, and the presence of melanosomes were used to determine whether the injured RPE was being repaired by the donor bone marrow.
Injury to the RPE recruits HSC/HPC-derived cells to incorporate into the RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs adopt RPE morphology, express melanosomes, and integrate into the RPE without cell fusion.
HSCs/HPCs can migrate to the RPE layer after physical or chemical injury and regenerate a portion of the damaged cell layer.
确定造血干细胞和祖细胞（HSCs/HPCs）在诱导损伤后是否能归巢至视网膜色素上皮（RPE）并使其再生。
将来自绿色荧光蛋白（gfp）转基因小鼠的富集HSCs/HPCs移植到经辐照的受体小鼠体内，以追踪骨髓来源的细胞。通过破坏布鲁赫膜并诱导血管内皮生长因子A（VEGFa）表达来促进新生血管形成，从而诱导物理损伤。还通过向野生型或白化C57Bl/6小鼠注射碘酸钠（40 mg/kg）来诱导RPE损伤。利用细胞形态、gfp表达、Y染色体的存在以及黑素小体的存在来确定受损的RPE是否由供体骨髓修复。
RPE损伤会募集HSC/HPC来源的细胞，使其整合到RPE层并分化为RPE表型。一部分HSCs/HPCs呈现RPE形态，表达黑素小体，并在不发生细胞融合的情况下整合到RPE中。
HSCs/HPCs在物理或化学损伤后可迁移至RPE层，并使部分受损细胞层再生。
