ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
This article is part of the Research TopicAdvancing Retinal Regeneration: The Role of Stem Cells in Therapy and InnovationView all articles
Degradable fibrin hydrogels for transplantation of iPSC-derived retinal pigment epithelial cell monolayers
Provisionally accepted
Alan Marmorstein1*
Brittni Scruggs1
Travis Knudsen1Matthew Hill1Francesca Kopp1
Emma Trncic1David Korda1Evan Atherton1Aubrey Berger1
Silvia C Finnemann2Jarel Gandhi1
Raymond Iezzi1- 1Mayo Clinic, Rochester, United States
- 2Fordham University, New York, United States
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Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We've shown that RPE can be grown on high concentration (>30mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 x 58.42 x 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 x 5.0 x 0.2mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37oC for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.
Keywords: Fibrin, Geographic Atrophy, iPSCs, Retinal Pigment Epithelium, Scaffold, Stem Cells
Received: 04 Nov 2025; Accepted: 16 Dec 2025.
Copyright: © 2025 Marmorstein, Scruggs, Knudsen, Hill, Kopp, Trncic, Korda, Atherton, Berger, Finnemann, Gandhi and Iezzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alan Marmorstein
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