Til bevillingsoversigt

Cell replacement therapy in the retina: solving immunogenicity and improving integration

Carlsbergfondets internationaliseringsstipendier

What

This research project aims at finding a way to replace diseased tissue in the retina, as a treatment for the vision-threatening disease, dry age-related macular degeneration (AMD). We will take a universal donor stem-cell line and differentiate it into functioning retinal pigment epithelial cells (RPE), a retinal cell-type that dies in patients with dry AMD, leading to vision loss. The RPE cells from the stem-cells will then be transplanted into the back of the retina to replace the lost RPE and preserve and restore vision.

The universal donor cell will eliminate the need for immunosuppression to avoid transplant rejection. To further ensure transplant survival, we will develop a nanomedicine with supporting factors, to be given with the transplant transplantation.

Why

AMD is the leading cause of blindness in people over the age of 50 in the industrialized world, and the number of patients is increasing due to the increase in life-expediency. Loss of vision has a devastating impact on the quality of life of the patient, despite this, there is currently no treatment against dry AMD. Cell replacement therapies have shown great promise, but poor transplant cell survival and the need for immunosuppression in transplant recipients, highly limit the potential of this treatment.

This research project focuses on overcoming these limitations to vision rescue. Additionally, loss of RPE is linked to other blinding diseases, e.g. retinitis pigmentosa, and knowledge obtained through this project can aid the development of treatments for these debilitating conditions.

How

We will grow RPE cells by differentiating the universal donor stem-cells through a three months long maturation culture and verify that the cells are fully developed into RPE by looking for expression of specific proteins and test the RPE-cells ability to recycle photoreceptor outer-segments.

The transplant's ability to avoid the host immune system will be evaluated by transplanting the cells into the retina of mice with a humanized immune system. The effect of the RPE transplantation in combination with the developed nanomedicine, on vision rescue, will be tested in a rat model of dry AMD.

SSR

I believe that it is important that we in science broaden our focus to not only prolong human life span but also improve the quality of life for people. Sight is one of our most important senses and loss of vision is truly debilitating for the patient’s independence, mobility and quality of life.

Additionally, it is important that we through free and independent research, and the communication of our results, can help keep the cost of new healthcare treatments at a level where it won’t only be accessible to a few people, but can benefit society as a whole.