The impact of chromosomal abnormalities in hPSC-derived retinal pigmented epithelial cells

Project Details


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.
Effective start/end date1/01/2231/12/25


  • retinal pigmented epithelial cells
  • Genome instability in human pluripotent stem cells
  • Differentiation impairment

Flemish discipline codes

  • Genetics
  • Stem cell biology