Subretinal Transplantation of Human Central Nervous System Stem Cells Stimulates Controlled Proliferation of Endogenous Retinal Pigment Epithelium.

RPE age related macular degeneration cell transplantation neural stem cells proliferation

Journal

Translational vision science & technology
ISSN: 2164-2591
Titre abrégé: Transl Vis Sci Technol
Pays: United States
ID NLM: 101595919

Informations de publication

Date de publication:
Jun 2019
Historique:
received: 03 01 2019
accepted: 26 03 2019
entrez: 28 6 2019
pubmed: 28 6 2019
medline: 28 6 2019
Statut: epublish

Résumé

The loss of retinal pigment epithelial (RPE) cells is a feature common to age-related macular degeneration (AMD) and retinitis pigmentosa (RP) and multiple early phase clinical trials are underway testing the safety of RPE cell replacement for these diseases. We examined whether transplantation of human neural stem cells into the subretinal space could enhance the endogenous proliferative capacity of the host RPE cell to regenerate. Human central nervous system stem cells (HuCNS-SC) were isolated from enzymatically treated brain tissue using flow cytometry. Pigmented dystrophic Royal College of Surgeons (RCS) and S334ter-4 rats treated with oral bromodeoxyuridine (BrdU) received a unilateral subretinal injection of 1.0 × 10 RCS rats that received transplantation of HuCNS-SC had significantly more (approximately 3-fold) Ki67-positive or BrdU-labelled host RPE cells adjacent to the HuCNS-SC graft than controls. Significantly increased host RPE cell proliferation as a result of HuCNS-SC transplantation also was confirmed in S334ter-line 4 transgenic rats with higher proliferation observed in animals with longer posttransplantation periods. These results suggest that controlled proliferation of endogenous RPE by HuCNS-SC may provide another mechanism by which RPE cell diseases could be treated. Engaging the capacity for endogenous RPE cell regeneration in atrophic diseases may be a novel therapeutic strategy for degenerative diseases of the RPE and retina.

Identifiants

pubmed: 31245172
doi: 10.1167/tvst.8.3.43
pii: TVST-18-1303
pmc: PMC6586077
doi:

Types de publication

Journal Article

Langues

eng

Pagination

43

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Auteurs

Trevor J McGill (TJ)

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.

Linda Osborne (L)

StemCells, Inc., Newark, CA, USA.

Bin Lu (B)

Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Jonathan Stoddard (J)

Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.

Stephen Huhn (S)

StemCells, Inc., Newark, CA, USA.

Ann Tsukamoto (A)

StemCells, Inc., Newark, CA, USA.
Current address: BOCO Silicon Valley, Palo Alto, CA, USA.

Alexandra Capela (A)

StemCells, Inc., Newark, CA, USA.

Classifications MeSH