CRISPR—Cas9 could allow ‘universal’ retinal cells for treating blindness

Researchers have found a way to enhance the production of retinal cells from ESCs, and also a method to allow them to remain undetected by the immune system.

Two high impact studies have been published by researchers from Karolinska Institutet (Solna, Sweden) and St Erik Eye Hospital (Stockholm, Sweden). The researchers discovered specific cell surface markers on retinal pigment epithelial (RPE) cells that can be used to isolate and purify retinal cells, as well as to optimize differentiation protocols. The same group from the Karolinska Institutet also used CRISPR—Cas9 to modify embryonic stem cells (ESCs) and allow them to hide from the immune system, in an effort to prevent rejection — the results of which were tested in rabbits.

The results have been published in Nature Communications and Stem Cell Reports. Together, the results from these studies could help treat age-related macular degeneration of the eye by allowing the mass production of allogeneic RPEs from ESCs, which can then be utilized in transplants.

“The finding has enabled us to develop a robust protocol that ensures that the differentiation of ESCs into RPE cells is effective and that there is no contamination of other cell types,” explained Fredrik Lanner (Karolinska Institutet). “We’ve now begun the production of RPE cells in accordance with our new protocol for the first clinical study, which is planned for the coming years.”

The risk of rejection adds complication when transplanting tissue generated from stem cells into a patient whose tissue does not match. To prevent this issue, research groups are working on developing universal cells, which hopefully will not trigger an immune response.

Researchers at Karolinska Institutet used CRISPR/Cas9 gene editing to remove HLA class I and class II molecules from the surface of ESCs. Usually, HLA class I and class II molecules are used by the immune system to identify them as endogenous or not. The modified ESCs missing these molecules were then differentiated into RPE cells.

The research team demonstrated that the modified RPE cells maintain their character and avoid the immune system’s T-cells without activating other immune cells or mutating. They also found that the rejection rate was delayed and considerably less compared to transplantation of regular RPE cells, when tested in rabbits.

“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,” concluded Anders Kvanta (Erik Eye Hospital).

The research is still in the early stages of development; however, the team will soon be examining the cells’ efficacy in clinical trials.

Sources: Plaza Reyes A, Petrus-Reurer S, Padrell Sánches S et al. Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells. Nat. Commun. 11, 1609 (2020).

Petrus-Reurer S, Winblad N, Kumar P et al. Generation of retinal pigment epithelial cells derived from human embryonic stem cells lacking human leukocyte antigen class I and II. Stem Cell Rep. doi: 10.1016/j.stemcr.2020.02.006 (2020).