2025-05-22 アメリカ国立衛生研究所(NIH)
Top image shows the scaffold-only, which served as a control. Bottom image shows how the scaffold with RPE regenerated the choriocapillaris (labeled red), the part of the eye that supplies the retina with oxygen and nutrients. Kapil Bharti, Ph.D.
<関連情報>
- https://www.nei.nih.gov/about/news-and-events/news/nih-scientists-test-animal-model-surgical-technique-improve-cell-therapy-dry-amd
- https://insight.jci.org/articles/view/179246
- https://www.science.org/doi/10.1126/scitranslmed.aat5580
- https://www.science.org/doi/10.1126/scitranslmed.aaw7624
iPSC-RPEパッチがブタの網膜変性モデルで光受容体を回復させ絨毛を再生させる iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model
Rohan Gupta, Irina Bunea, Bruno Alvisio, Francesca Barone, Rishabh Gupta, Dara Baker, Haohua Qian, Elena Daniele, Casey G. Contreary, Jair Montford, Ruchi Sharma, Arvydas Maminishkis, Mandeep S. Singh, Maria Teresa Magone De Quadros Costa, Amir H. Kashani, Juan Amaral, and Kapil Bharti
JCI Insight Published: May 22, 2025
DOI:https://doi.org/10.1172/jci.insight.179246
Abstract
Dry age-related macular degeneration (AMD) is a leading cause of untreatable vision loss. In advanced cases, retinal pigment epithelium (RPE) cell loss occurs alongside photoreceptor and choriocapillaris degeneration. We hypothesized that an RPE-patch would mitigate photoreceptor and choriocapillaris degeneration to restore vision. An induced pluripotent stem cell–derived RPE (iRPE) patch was developed using a clinically compatible manufacturing process by maturing iRPE cells on a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold. To compare outcomes, we developed a surgical procedure for immediate sequential delivery of PLGA-iRPE and/or PLGA-only patches in the subretinal space of a pig model of laser-induced outer retinal degeneration. Deep learning algorithm-based optical coherence tomography (OCT) image segmentation verified preservation of the photoreceptors over the areas of PLGA-iRPE–transplanted retina and not in laser-injured or PLGA-only–transplanted retina. Adaptive optics imaging of individual cone photoreceptors further supported this finding. OCT-angiography revealed choriocapillaris regeneration in PLGA-iRPE– and not in PLGA-only–transplanted retinas. Our data, obtained using clinically relevant techniques, verified that PLGA-iRPE supports photoreceptor survival and regenerates choriocapillaris in a laser-injured pig retina. Sequential delivery of two 8 mm2 transplants allows for testing of surgical feasibility and safety of the double dose. This work allows one surgery to treat larger and noncontiguous retinal degeneration areas.
臨床グレードの幹細胞由来網膜色素上皮パッチがネズミとブタの網膜変性を救う Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs
Ruchi Sharma, Vladimir Khristov, Aaron Rising, Balendu Shekhar Jha, […] , and Kapil Bharti
Science Translational Medicine Published:16 Jan 2019
DOI:https://doi.org/10.1126/scitranslmed.aat5580
A pipeline for retinal stem cell therapy
Autologous induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) transplantation has been shown to improve visual function in animal models of age-related macular degeneration (AMD) and is currently being tested in human patients. However, oncogenic mutations might occur during the cell reprogramming process. Now, Sharma et al. used CD34+ peripheral blood cells from patients with AMD to generate oncogenic mutation-free iPSCs. These cells were used for the production of clinical-grade RPE cell patches. Transplantation of the RPE patches in rodent and pig models of retinal degeneration showed therapeutic effects. The authors suggest that the production process presented here might accelerate the development of safer iPSC-derived stem cell therapies.
Abstract
Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.
