Journal article
Biocompatibility of Human Induced Pluripotent Stem Cell-Derived Retinal Progenitor Cell Grafts in Immunocompromised Rats
Cell transplantation, Vol.31
01/01/2022
DOI: 10.1177/09636897221104451
PMCID: PMC9247396
PMID: 35758274
Abstract
Loss of photoreceptor cells is a primary feature of inherited retinal degenerative disorders including age-related macular degeneration and retinitis pigmentosa. To restore vision in affected patients, photoreceptor cell replacement will be required. The ideal donor cells for this application are induced pluripotent stem cells (iPSCs) because they can be derived from and transplanted into the same patient obviating the need for long-term immunosuppression. A major limitation for retinal cell replacement therapy is donor cell loss associated with simple methods of cell delivery such as subretinal injections of bolus cell suspensions. Transplantation with supportive biomaterials can help maintain cellular integrity, increase cell survival, and encourage proper cellular alignment and improve integration with the host retina. Using a pig model of retinal degeneration, we recently demonstrated that polycaprolactone (PCL) scaffolds fabricated with two photon lithography have excellent local and systemic tolerability. In this study, we describe rapid photopolymerization-mediated production of PCL-based bioabsorbable scaffolds, a technique for loading iPSC-derived retinal progenitor cells onto the scaffold, methods of surgical transplantation in an immunocompromised rat model and tolerability of the subretinal grafts at 1, 3, and 6 months of follow-up (n = 150). We observed no local or systemic toxicity, nor did we observe any tumor formation despite extensive clinical evaluation, clinical chemistry, hematology, gross tissue examination and detailed histopathology. Demonstrating the local and systemic compatibility of biodegradable scaffolds carrying human iPSC-derived retinal progenitor cells is an important step toward clinical safety trials of this approach in humans.
Details
- Title: Subtitle
- Biocompatibility of Human Induced Pluripotent Stem Cell-Derived Retinal Progenitor Cell Grafts in Immunocompromised Rats
- Creators
- Ian C HanLaura R BohrerKatherine N Gibson-CorleyLuke A WileyArwin ShresthaBrynnon E HarmanChunhua JiaoElliott H SohnRion WendlandBrittany N AllenKristan S WorthingtonRobert F MullinsEdwin M StoneBudd A Tucker
- Resource Type
- Journal article
- Publication Details
- Cell transplantation, Vol.31
- DOI
- 10.1177/09636897221104451
- PMID
- 35758274
- PMCID
- PMC9247396
- ISSN
- 0963-6897
- eISSN
- 1555-3892
- Grant note
- DOI: 10.13039/100000053, name: National Eye Institute, award: P30 EY025580; DOI: 10.13039/100000053, name: National Eye Institute, award: R01 EY 024605; DOI: 10.13039/100012201, name: Elmer and Sylvia Sramek Charitable Trust; DOI: 10.13039/100000053, name: National Eye Institute, award: R01 EY033331
- Language
- English
- Date published
- 01/01/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Fraternal Order of Eagles Diabetes Research Center; Chemical and Biochemical Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9984269059202771
Metrics
27 Record Views