Efficient Differentiation of Retinal Pigment Epithelial Cells from hESC
Principal Investigator
Project Goals
Retinal pigment epithelial (RPE) cells are damaged in age-related macular degeneration (AMD), so Dr. Wei Liu and colleagues aim to efficiently generate RPE cells from the H1 human embryonic stem cell (hESC) cultures by adding active regulatory molecules to the cell-culture medium. This program is based on the recent findings that these active regulatory molecules promote embryonic RPE development. The team plans to develop a more efficient protocol for the generation of RPE cells for a future stem cell-based strategy in treating AMD.
Project Summary
Dr. Wei Liu and colleagues aim to identify the regulatory molecules that promote the generation of RPE cells by using cultures of human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs). Liu plans to use the H1 hESC line, which is among the most extensively studied and characterized.
AMD is characterized by progressive dysfunction and degeneration of the aging RPE and photoreceptor (light-detecting) cells in the macular region, leading to impairment and loss of central, high-acuity vision. RPE cells closely interact with photoreceptors and are crucial for photoreceptor functions and survival. While anti-VEGF eye injection treatments have been developed for wet AMD, no effective treatment is available for dry AMD.
Stem cell-based strategies in treating and modeling of AMD are emerging as a new frontier in this field. The current protocols for the generation of RPE cells in hESC or hiPSC cultures are still inefficient. More efficient generation of RPE cells from either hESCs or iPSCs cultures are needed to advance the potential clinical applications of current stem cell-based research.
Liu has recently identified the key pathways that regulate embryonic RPE development; manipulating these pathways could help improve the efficiency of RPE cell production in hESC- or hiPSC-derived cultures. The novelty of this project is to determine the roles of these regulatory molecules in stimulating hESC or hiPSC to change into RPE cells, which has not been evaluated before. This project helps to bring the field closer to a potential stem cell-based strategy for treatment of AMD, in which RPE cells are impaired and degenerated.
Publications
Lowe A, Harris R, Bhansali P, Cvekl A, Liu W. Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid. Stem Cell Reports. 2016 May 10;6(5):743-56. doi: 10.1016/j.stemcr.2016.03.011. Epub 2016 Apr 28. 
Shi J, Dong Y, Cui MZ, Xu X. Lysophosphatidic acid induces increased BACE1 expression and Aβ formation. Biochim Biophys Acta. 2013 Jan;1832(1):29-38.
Li T, Zeng L, Gao W, Cui MZ, Fu X, Xu X. PSAP induces a unique Apaf-1 and Smac-dependent mitochondrial apoptotic pathway independent of Bcl-2 family proteins. Biochim Biophys Acta. 2012 Nov 30.
Zeng L, Li T, Xu DC, Liu J, Mao G, Cui MZ, Fu X, Xu X. Death receptor 6 induces apoptosis not through type I or type II pathways, but via a unique mitochondria-dependent pathway by interacting with Bax protein. J Biol Chem. 2012
Aug 17;287(34):29125-33
Mao G, Cui MZ, Li T, Jin Y, Xu X. Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment. J Neurochem. 2012 Dec;123(5):837-44.
First published on: July 10, 2012
Last modified on: November 13, 2024