Choosing the right cells for cell replacement therapy

Research details

  • Type of funding: Early Career Investigator Award
  • Grant Holder: Dr Jörn Lakowski
  • Institute: UCL Institute of Child Health
  • Region: London
  • Start date: January 2015
  • End Date: December 2017
  • Priority: Treatment
  • Eye Category: Inherited retinal


Loss of the light-sensitive cells (photoreceptors) from the retina at the back of the eye can cause severe sight loss or blindness. Current treatments, where there are any, can’t give people their sight back – they can only delay the start of sight loss, or slow it down.

Previous research in animals has shown that transplanting new cells into the eye could perhaps restore sight. So the research team is trying to work out the best way to prepare cells from human donors. Stem cells can become most types of cell in the body and it’s vital that only the right type of cell is transplanted to make sure any surgery is both safe and works as intended.

In this project he researchers will develop a way to select the right cells by looking for proteins called biological markers, or ‘biomarkers’ found on the surface of cells. They will:

  • Test for known biomarkers and look for new ones
  • Develop methods to sort the right kind of stem cell from other stem cells
  • Transplant human stem cells into an animal model
Results from the study will give us clearer procedure for successful photoreceptor cell replacement therapy. This is the background work needed for future human clinical trials in conditions such as age-related macular degeneration and inherited retinal disorders.
  • Scientific summary

    Identification of biomarkers for selection of transplantation-competent human photoreceptor precursors for retinal cell therapy.

    The loss of photoreceptors due to retinal degeneration is a major cause of blindness in the developed world. While no effective treatment is currently available, replacement of lost photoreceptors, using in vitro generated donor cells, may be a feasible treatment option in the future.

    The research team has demonstrated that immature rod photoreceptor cells can be introduced into the normal and diseased rodent retina via sub-retinal transplantation. Grafted rods, migrated into the host outer nuclear layer, completed maturation and connected to the existing retinal circuitry. Rod-mediated vision was restored in dysfunctional retinae as demonstrated by improved optomotor head tracking responses and visually guided behaviours in treated animals.

    Safety and efficacy of this approach in a clinical setting depends on stringent selection of the donor cells. As genetic modification of donor cells is not desirable for therapy the team has developed a selection protocol for efficient isolation of correctly staged mouse rod precursors using endogenously expressed, cell surface markers.
    The aim of this project is to establish an equivalent cell sorting strategy for the isolation of transplantation-competent rod and cone photoreceptor precursors (PPr) from human stem cell sources for use in retinal cell therapy. It will (1) test biomarkers previously identified in the murine system, (2) identify new biomarkers by surveying the complete transcriptome and cell surface proteome profile of developing human rod and cone photoreceptors, (3) develop protocols for isolation of human PPr from induced pluripotent stem cells and (4) test integration efficacy of in vitro generated PPr in pre-clinical transplantation experiments.