From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium
Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC)...
Saved in:
Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 23; pp. 8518 - 8523 |
---|---|
Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
10.06.2014
National Acad Sciences |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease. |
---|---|
Bibliography: | http://dx.doi.org/10.1073/pnas.1324212111 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited* by Nicole M. Le Douarin, Centre National de La Recherche Scientifique, Gif-sur-Yvette, France, and approved May 2, 2014 (received for review December 31, 2013) Author contributions: S.R., J.-A.S., and O.G. designed research; S.R., A.T., A.S., C.N., and O.G. performed research; G.O., W.H., E.F.N., and C.M. contributed new reagents/analytic tools; S.R., A.T., C.M., and O.G. analyzed data; and S.R. and O.G. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1324212111 |