Publishing in Stem Cell Reports, a new University of Wisconsin-Madison study has developed a novel method to generate photoreceptor-dominant retinal organoids (ROs) from porcine induced pluripotent stem cells (piPSCs). The advancement provides a crucial preclinical model for studying retinal degenerative diseases (RDDs) and developing potential cell-based therapies.
While human pluripotent stem cells (hPSCs) have been successfully used to create photoreceptors for transplantation in retinal degenerative disease treatment, preclinical animal models are needed to test these therapies before clinical use. Because the pig retina closely resembles the human retina in size, structure, and function, this makes it a valuable model for retinal disease research and transplantation studies.
The research team adapted an existing human PSC-RO differentiation protocol to match the faster developmental timeline of pigs, resulting in the efficient and scalable production of piPSC-derived retinal organoids (piPSC-ROs).
Using optimized conditions, piPSC-ROs were produced consistently and in large quantities, and the organoids were found to contain highly organized photoreceptor cells, mimicking natural retinal development. Early-stage piPSC-ROs contained retinal progenitor cells (RPCs), retinal ganglion cells (RGCs), and early cone photoreceptors. By day 120 of development, both rod and cone photoreceptors were present, along with Müller glia, bipolar cells, and amacrine cells.
The piPSC-ROs developed similarly to human-derived retinal organoids, sharing key molecular and cellular features, and single-cell RNA sequencing confirmed that porcine and human ROs have highly conserved gene expression patterns, particularly in photoreceptors and bipolar cells.
This ability to grow photoreceptor-rich ROs from piPSCs opens up new possibilities for retinal transplantation in pig models, and could provide a more reliable preclinical testing environment than human-to-animal transplants, which often face immune rejection challenges.
The study marks a significant step in stem cell-based retinal therapy research. By providing a reproducible and efficient method for generating porcine-derived retinal organoids, researchers can now further explore the molecular mechanisms of retinal development, paving the way for personalized regenerative medicine.
