Format

Send to

Choose Destination
Stem Cells. 2017 Mar;35(3):572-585. doi: 10.1002/stem.2513. Epub 2016 Oct 26.

Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism.

Author information

1
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
2
Department of Pharmacology, Creighton University, Omaha, Nebraska, USA.
3
Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA.
4
Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
5
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Abstract

Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585.

KEYWORDS:

Chemically defined medium; Directed differentiation; Embryonic stem cells; Glaucoma; Induced pluripotent stem cells; Retinal ganglion cells

PMID:
27709736
PMCID:
PMC5330843
DOI:
10.1002/stem.2513
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center