A research team headed by Dr. David Gamm of the University of Wisconsin-Madison is about to take a big step forward in developing a vision-restoring, stem-cell-based therapy for people with advanced retinal diseases. With $900,000 in funding from the Foundation’s Translational Research Acceleration Program (TRAP), the team is constructing a two-layered patch of cells to replace retinal tissue lost from conditions like retinitis pigmentosa and age-related macular degeneration.
The patch, Dr. Gamm believes, is the best strategy for reconstructing the retina when multiple cell types have succumbed to disease. Building on his previous TRAP-funded research, he is confident that this approach will get him closer to a clinical trial for a human therapy.
“We started our first TRAP grant in 2008 just after induced pluripotent stem cells (iPSCs) — stem cells derived from skin or blood — were first created,” Dr. Gamm explains. “At the time, no one had even shown that iPSCs could be made into retinal cells. We and others have succeeded in doing that. The continuing challenge has been to get the transplanted cells to survive the hostile conditions of the diseased retina, arrange themselves appropriately and make the necessary connections to restore vision. I believe we have the right plan to make tremendous progress toward that goal.”
Dr. Gamm’s collaborators — Drs. Dennis Clegg, of the University of California, Santa Barbara; James Thomson, of the Morgridge Institute for Research; and Derek Hei, of the University of Wisconsin-Madison — will create a patch consisting of two layers of stem cells. One layer will serve as the precursors to vision-enabling rods and cones, or photoreceptors; once transplanted, they will mature into photoreceptors. The other layer will consist of mature retinal pigment epithelial (RPE) cells, which provide waste disposal and nutrition for photoreceptors. A thin plastic film developed by Dr. Clegg’s group will serve as a structural backbone for the patch. A biodegradable gel will protect the cells and hold the layers together.
“In many retinal diseases, both RPE and photoreceptors are lost and need to be replaced,” says Dr. Gamm. “We don’t want to transplant an unstructured mix of RPE and photoreceptors, because they aren’t likely to integrate and function properly, especially in a retina that’s suffered significant degeneration. Our patch — a pre-formed structure that better resembles a natural retina — should give the cells a much better chance of surviving and providing vision.”
Dr. Gamm’s group is also using funds from the Foundation grant to create lines of iPSCs from “super donors,” people whose cells and tissues provide an immune match for a significant percentage of the general public. When properly matched with the recipient, the cells are less likely to be rejected. The team’s goal is to have an “off-the-shelf” iPSC inventory that can be used to create patches for virtually any patient, regardless of the disease or immune system profile. To accomplish this important goal, and benefit the largest number of people possible, Dr. Gamm’s group has partnered with the Madison-based company Cellular Dynamics International and the Waisman Biomanufacturing Facility.
While iPSCs can be derived from each patient on a case-by-case basis, Dr. Gamm says the super-donor solution is technically simpler, less costly and may work just as effectively. His research will help bear out this approach’s feasibility and benefits.
Dr. Gamm acknowledges that he and his colleagues will learn as much from the research process as its final outcomes. “We’re pushing the envelope by transplanting multiple cells types,” he says. “But along the way, we will answer several important questions: Can we make cells that align correctly with one another? Do they make synapses and hook up to other cells? What is the best way to transplant them, keep them healthy and promote their integration within a diseased retina? It’s not an easy task, but neither was making those first retinal cells from iPSC back in 2008. We reached our goals then, and I am confident we’ll keep moving forward.”
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