The impact of chromosomal abnormalities in hPSC-derived retinal pigmented epithelial cells
Description: Age-related macular degeneration (AMD) is the leading cause of blindness and vision impairment worldwide and is a result of the degeneration of the retinal pigment epithelium (RPE). The most novel cell therapy to effectively cure AMD is based on the use of human pluripotent stem cells (hPSC) to make RPE for transplantation, and the first clinical trials yielded promising results. However, hPSC kept in culture acquire genetic abnormalities. We still have a poor understanding on the functional consequences of these abnormalities, which represents one of the major current bottlenecks for the safe transition of these therapies to the clinic. In our study, we will focus on understanding the impact of a chromosomal abnormalities on the differentiation of hPSC into RPE. We will research the functional effects of the chromosomal abnormalities most commonly found in hPSC lines worldwide, as well as of mosaic abnormalities that appear randomly in subpopulations of cells in culture. We will study the transcriptome of these cells to predict the impact of genetic abnormalities on the cells, and validate these findings with functional studies. This project will provide key information for a realistic risk-assessment of chromosomal abnormalities in the clinical translation of hPSC-derived RPE and novel insight to the role aneuploidy in modulating or altering the course of hPSC differentiation.
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: grant
Funder scheme: FWO research project (including WEAVE projects)
Start date: 2022-01-01
End date: 2025-12-31
Investigator: Claudia Spits
Institution: FWO
Funded outputs count: 0
Funder award ID: G071322N
OpenAlex ID: G6081747752