Advances in the production of retinal cells for treatment of blindness
Age-related macular degeneration of the eye is the most common cause of blindness in elderly people. This loss of vision is caused by the death of the photoreceptors (sticks and cones) resulting from the degeneration and death of the underlying retinal pigment epithelial (RPE) cells, which provide vital nourishment to the rods and cones. Renewed RPE cell transplantation could be a possible future treatment.
Working with colleagues at St Erik Eye Hospital, researchers at Karolinska Institutet have now found specific markers on the surface of the RPE cells that can be used to isolate and purify these retinal cells. The results are published in Nature Communications.
Planning the first clinical study
“The findings have enabled us to develop a robust protocol that ensures that the differentiation of embryonic stem cells into RPE cells is effective and that there is no contamination of other cell types,” says Chief Investigator Fredrik Lanner, Researcher at the Department of Clinical Science, Intervention and Technology and the Ming Wai Lau Center for Reparative Medicine at the Karolinska Institute.
One obstacle when transplanting tissue generated from stem cells is the risk of rejection, which occurs if transplantation antigens of the donor and patient tissue differ. Research groups around the world are therefore working on creating what are known as universal cells, which ideally will not trigger an immune response.
Cells that avoid the immune system
In a study published in Stem Cell Reports the same group at Karolinska Institutet created embryonic stem cells able to hide from the immune system. Using CRISPR/Cas9 gene editing, they removed certain molecules, HLA class I and class II, which sit on the surface of the stem cells as a means by which the immune system can identify them as endogenous or not. The stem cells lacking these molecules were then differentiated into RPE cells.
The researchers have been able to show that the modified RPE cells retain their character, that no harmful mutations appear in the process and that the cells can avoid the immune system’s T cells without activating other immune cells. The rejection response was also significantly less and more delayed than after the transplantation of regular RPE cells, the surfaces of which still possess HLA molecules.
An important initial step
“The research is still in an early stage, but this can be an important initial step towards creating universal RPE cells for the future treatment of age-related macular degeneration,” says joint last author Anders Kvanta, adjunct professor at the Department of Clinical Neuroscience and consultant at St Erik Eye Hospital.