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Proteomics. 2018 Dec 4:e1800213. doi: 10.1002/pmic.201800213. [Epub ahead of print]

In vitro and in vivo Proteomic Comparison of Human Neural Progenitor Cell-Induced Photoreceptor Survival.

Author information

1
Department of Biomedical Sciences, Cedars-Sinai Medical Center.
2
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center.
3
Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars-Sinai Medical Center.
4
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles.

Abstract

Retinal degenerative diseases are some of the leading causes of blindness with few treatments. Various cell-based therapies have aimed to slow the progression of vision loss by preserving light-sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment will lead to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co-culture system of retinas and hNPCs was developed. Less cell death occurred in RCS retinal tissue co-cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identified NRF2-mediated oxidative response signaling as an hNPC-induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications. This article is protected by copyright. All rights reserved.

KEYWORDS:

Human neural progenitor cells; neuroprotection; retinal degeneration; stem cells; transplantation

PMID:
30515959
DOI:
10.1002/pmic.201800213

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