Researchers report on the generation of transplantable retinal cells from cultured pig induced pluripotent stem cells (iPSCs). The University of Louisville and University of Missouri team subsequently confirmed these cells could integrate into the damaged retina of experimental pigs.
The researchers claim their results lay the foundation for future studies using the pig as a model for retinal stem cell transplantation. Their work is published in Stem Cells in a paper titled “Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina.”
Studies in mice have demonstrated the feasibility of retinal cell transplantation therapy for human retinal disease, but in contrast with the human eye, the mouse retina is rod-dominant and lacks a macula, which means the animal is not an ideal physiological or anatomical model for extrapolating to humans, explains the University of Louisville’s Douglas Dean, Ph.D., and colleagues.
In contrast, the swine eye contains a cone-dominant central visual streak analogous to the macula and is thus a closer anatomical and physiological match to the human eye than the murine model. Unfortunately, use of the swine retina as an experimental model for stem cell transplantation has been hampered by the fact that embryonic stem cells have not been isolated from the pig and attempts have not been made to differentiate swine iPSCs into photoreceptor cell lines.
As an initial step toward generating a swine model for retinal stem cell transplant, Dr. Dean’s team has now developed an efficient protocol for differentiation of swine iPSC into the rod photoreceptor lineage and shown these cells are capable of integrating into the outer nuclear layer of retinas depleted of rod photoreceptors. Their achievement hinged on a two-step protocol for triggering rod photoreceptor differentiation from swine iPSCs, involving suspension culture of the cells as embryoid bodies, followed by adherent culture on an extracellular matrix.
Three weeks after transplanting these cells into the rod cell-depleted retinas of experimental animals, engrafted rod cells were evident in the outer nuclear layer where photoreceptors normally reside, and a portion of the transplanted cells had generated projections resembling outer segments.
Although only a small section of retina was transplanted in the published studies, the researchers hope the achievement will ultimately mean the pig can be used as a more physiologically relevant model for studying human degenerative eye diseases and developing stem cell transplantation technologies.