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Guochun Chen, Desiree Cyr, Marie A. Shatos, Michael Young, Kameran Lashkari; Comparative Analysis Of Human Persistent Fetal Vascular Cells And Retinal Progenitor Cells As Candidates For Inner Retina Transplantation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2239.
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© ARVO (1962-2015); The Authors (2016-present)
Various neural stem or progenitor cells have been tested for their potential for integration into the host retina after transplantation. Our laboratory has previously shown that cells isolated from human persistent fetal vasculature (hPFV) membranes are retinal progenitor cells that differentiate into retinal neurons after intravitreal transplantation. To further elucidate the mechanisms involved in xenograft inner retinal transplantation, we compared the behavior of hPFVs with that of human retinal progenitor cells (hRPCs). hRPCs were obtained from 16-18 week gestation fetal retina
hPFV cells and hRPCs were subjected to immunocytochemistry and qRT-PCR analysis for protein and gene expression of progenitor and neuronal markers. After labeling with AAV2-eGFP or retro-eGFP, cells were transplanted into the vitreous of C57BL/6J or SCID mice and observed for up to 3 weeks. Eyes were subjected to immunohistochemistry and confocal imaging to evaluate the outcome of transplantation.
Both cultured hPFVs and hRPCs highly expressed neural progenitor markers (Nestin, Ki67, Pax6 and beta-tubulinIII). hPFVs preferentially expressed retinal ganglion and neuronal markers including Brn3a and synapse-related genes. hRPCs exhibited a photoreceptor progenitor phenotype with expression of recoverin and rhodopsin. In C57BL/6J mice both cell types survived intravitreal transplantation for the first 3 days, but had decreased survival by 7 days. Cell survival was dramatically increased in SCID Robust migration of hPFVs into inner retina was observed by 3 weeks. Some hPFV cells exhibited a neuronal morphology and expressed beta-III-tubulin after differentiation with retinoic acid. hRPCs on the other hand rested on the inner retinal surface with little penetration the inner retina.
Our data indicate that hPFVs and hRPCs are both retinal progenitors with different retinal gene and protein expression profiles. Survival analysis after transplantation indicates that the host immune system may play an important role in the success of cell transplantation. hPFVs adopts an energetic migratory phenotype and may be a better candidate cell line for intravitreal transplantation of inner retina. Further experiments are necessary to investigate the mechanisms by which hPFVs overcome the natural barriers of the inner retina.
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