Porcine Stem Cells Advance Retinal Organoid Research for Vision Restoration

Breakthrough in Retinal Organoid Generation

A new study published in Stem Cell Reports describes a major advancement in retinal organoid research using porcine induced pluripotent stem cells (piPSCs). By modifying established protocols for human retinal organoids (ROs), researchers achieved efficient, reproducible generation of photoreceptor-dominant piPSC-derived ROs, providing a crucial tool for preclinical studies. These organoids closely mimic the cellular and molecular features of human retinal tissue, offering a reliable model for developing vision-restoring therapies.

What’s New?

Scientists from the University of Wisconsin-Madison and the University of Calgary successfully adapted a human PSC-RO differentiation protocol to align with the 16-week gestational timeline of pigs—less than half the human gestational period. This adaptation led to an average yield of 217 ± 19 ROs per differentiation, a significant improvement over previous attempts that generated fewer than four ROs per 6-well plate using unmodified human protocols​.

These retinal organoids were extensively characterized using immunocytochemistry (ICC), flow cytometry, and single-cell RNA sequencing (scRNA-seq). The results revealed:

• By day 40: The presence of early photoreceptor precursors, retinal ganglion cells (RGCs), and retinal progenitor cells (RPCs).
• By day 120: A highly organized outer neuroepithelium with structurally mature rods and cones, as well as Müller glia, amacrine cells, and bipolar cells.
• By day 190: A layered retinal structure similar to adult porcine retina, featuring outer nuclear layers (ONL), outer plexiform layers (OPL), and inner nuclear layers (INL)​.

Why It Matters?

Retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration (AMD) lead to photoreceptor loss, a primary cause of blindness worldwide. Although human stem-cell-derived retinal transplants are promising, their use in animal models is limited due to immunological rejection and evolutionary differences that hinder functional integration.

Pigs provide a powerful alternative model due to their:

• Large-eye size, allowing for surgical techniques identical to human procedures.
• Retinal structure and photoreceptor distribution that closely resemble human anatomy.
• Reduced immune rejection risk when using porcine-derived cells instead of human xenografts​.

This study provides a scalable, reproducible system for generating piPSC-derived retinal organoids, enabling species-matched cell transplantation for testing new treatments in porcine models before advancing to human clinical trials.