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Trevor J McGill, Jonathan Stoddard, Bin Lu, Ann Tsukamoto-Weissman, Stephen huhn, Linda Osborne, Alexandra Capela; Subretinal transplantation of Human Central Nervous System Stem Cells stimulates controlled proliferation of endogenous retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2887.
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© ARVO (1962-2015); The Authors (2016-present)
Cell transplantation is a promising prospective therapy for the treatment of retinal degenerative diseases including age related macular degeneration (AMD) and retinitis pigmentosa (RP). RPE cell loss is a feature common to both AMD and RP and multiple early phase clinical trials are underway testing the safety of RPE cell replacement with the intent of rescuing vulnerable adjacent retina. The purpose of this study was to determine whether transplantation of human neural stem cells into the subretinal space could enhance the endogenous proliferative capacity of the host RPE cell to self-renew.
Human Central Nervous System Stem Cell (HuCNS-SC) populations positive for CD133 and CD224 were isolated from enzymatically treated brain tissue using flow cytometry. Pigmented dystrophic RCS and S334ter-4 rats treated with oral Bromodeoxyuridine (BrdU) received a unilateral sub-retinal injection of 1.0x105 HuCNS-SC cells at either P21 or P60. Animals were sacrificed at P90, P120 and P150 time points. Eyes were fixed in 2% paraformaldehyde and processed for cryostat sectioning. Sections were immunostained with Stem101, Ku80, RPE65 OTX1/2, BrdU, and CRALBP antibodies and analyzed via confocal microscopy.
In RCS rats that received transplantation of HuCNS-SC, there was a significant increase in the number of Ki67 positive host RPE cells adjacent to the HuCNS-SC graft. BrdU labeling was then used in RCS rats to identify all proliferating RPE cells from the day of transplantation until sacrifice, which also revealed a significant increase in proliferating host RPE in the cell-treated group compared to controls. In both cases, increased proliferation was approximately 3-fold over controls. Significantly increased host RPE cell proliferation as a result of HuCNS-SC transplantation was also confirmed in S334ter-line 4 transgenic rat with higher proliferation observed in animals with longer post-transplantation periods.
These results suggest that controlled proliferation of endogenous RPE by HuCNS-SC may provide another mechanism by which of RPE cell diseases could be treated.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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