Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa
Purpose: To explore the safety and efficacy of the allogeneic induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration. Design: Single-arm, open-label, interventional study. Participants: Three eyes from 3 patients clinica...
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Elsevier
2025-07-01
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| author | Daiki Sakai, MD Michiko Mandai, MD, PhD Yasuhiko Hirami, MD, PhD Midori Yamamoto, BA Shin-ichiro Ito, MD, PhD Saori Igarashi, MD Satoshi Yokota, MD, PhD Hirofumi Uyama, MD, PhD Masashi Fujihara, MD, PhD Akiko Maeda, MD, PhD Motoki Terada, BS Mitsuhiro Nishida, MS Yumiko Shibata, MS Naoko Hayashi, MS Kyoko Iseki, MA Takuya Miura, MS Keisuke Kajita, MD, PhD Masaaki Ishida, MD, PhD Sunao Sugita, MD, PhD Tadao Maeda, MD, PhD Masayo Takahashi, MD, PhD Yasuo Kurimoto, MD, PhD |
| author_facet | Daiki Sakai, MD Michiko Mandai, MD, PhD Yasuhiko Hirami, MD, PhD Midori Yamamoto, BA Shin-ichiro Ito, MD, PhD Saori Igarashi, MD Satoshi Yokota, MD, PhD Hirofumi Uyama, MD, PhD Masashi Fujihara, MD, PhD Akiko Maeda, MD, PhD Motoki Terada, BS Mitsuhiro Nishida, MS Yumiko Shibata, MS Naoko Hayashi, MS Kyoko Iseki, MA Takuya Miura, MS Keisuke Kajita, MD, PhD Masaaki Ishida, MD, PhD Sunao Sugita, MD, PhD Tadao Maeda, MD, PhD Masayo Takahashi, MD, PhD Yasuo Kurimoto, MD, PhD |
| author_sort | Daiki Sakai, MD |
| collection | DOAJ |
| description | Purpose: To explore the safety and efficacy of the allogeneic induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration. Design: Single-arm, open-label, interventional study. Participants: Three eyes from 3 patients clinically diagnosed with RPE impairment disease; 1 patient had dry age-related macular degeneration (AMD), and remaining 2 patients had MERTK-associated retinitis pigmentosa. Intervention: Allogeneic iPSC-derived RPE strip transplantation was performed by a 25-gauge pars plana vitrectomy. The RPE strips were prepared by incubating iPSC-derived RPE cells in 2-mm-wide grooves in the mold. Artificial retinal detachment was generated using a 38-gauge subretinal cannula, and the RPE strips were injected into the retinal bleb using a 31-gauge cannula with the maximum graft dose limited to 2 strips. Main Outcome Measures: The reduction of RPE abnormal area by the engraftment of transplanted allogeneic iPSC-derived RPE cells, which was measured by analyzing fluorescein angiography with an automated evaluation program at pretransplantation and up to 52 weeks posttransplantation. Results: The primary endpoint of reducing abnormal areas of RPE through the survival of the transplanted graft cells was achieved in all patients at 52 weeks posttransplantation. Visual function assessments confirmed significant vision-related quality of life improvement and potential retinal sensitivity restoration in 1 patient with dry AMD. The successful subretinal delivery of the iPSC-derived RPE strips was confirmed during and immediately after surgery. The engraftment of RPE cells migrated out from the strips was observed using polarization-sensitive OCT specifically and visualized as characteristic hexagonal cells via adaptive optics imaging in all patients. While no serious adverse events occurred, suspected immune reactions to graft cells and epiretinal membrane formation were observed in 1 patient each. Conclusions: A decrease in the RPE abnormal area by reliable delivery of allogeneic iPSC-derived RPE strips was achieved in all 3 cases with no serious adverse events. Further long-term studies and larger cohorts with better preoperative vision are warranted to evaluate the safety and efficacy of RPE strip transplantation. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| format | Article |
| id | doaj-art-d22e50fd7a2244e7b8b9778fca9f2e16 |
| institution | OA Journals |
| issn | 2666-9145 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj-art-d22e50fd7a2244e7b8b9778fca9f2e162025-08-20T02:17:41ZengElsevierOphthalmology Science2666-91452025-07-015410077010.1016/j.xops.2025.100770Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis PigmentosaDaiki Sakai, MD0Michiko Mandai, MD, PhD1Yasuhiko Hirami, MD, PhD2Midori Yamamoto, BA3Shin-ichiro Ito, MD, PhD4Saori Igarashi, MD5Satoshi Yokota, MD, PhD6Hirofumi Uyama, MD, PhD7Masashi Fujihara, MD, PhD8Akiko Maeda, MD, PhD9Motoki Terada, BS10Mitsuhiro Nishida, MS11Yumiko Shibata, MS12Naoko Hayashi, MS13Kyoko Iseki, MA14Takuya Miura, MS15Keisuke Kajita, MD, PhD16Masaaki Ishida, MD, PhD17Sunao Sugita, MD, PhD18Tadao Maeda, MD, PhD19Masayo Takahashi, MD, PhD20Yasuo Kurimoto, MD, PhD21Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan; Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan; Correspondence: Daiki Sakai, MD, Department of Ophthalmology, Kobe City Eye Hospitsal, 2-1-8 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University, Graduate School, Tokushima, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Toyama University, Toyama, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; VCCT Inc., Kobe, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan; Yasuo Kurimoto, MD, PhD, Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.Purpose: To explore the safety and efficacy of the allogeneic induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration. Design: Single-arm, open-label, interventional study. Participants: Three eyes from 3 patients clinically diagnosed with RPE impairment disease; 1 patient had dry age-related macular degeneration (AMD), and remaining 2 patients had MERTK-associated retinitis pigmentosa. Intervention: Allogeneic iPSC-derived RPE strip transplantation was performed by a 25-gauge pars plana vitrectomy. The RPE strips were prepared by incubating iPSC-derived RPE cells in 2-mm-wide grooves in the mold. Artificial retinal detachment was generated using a 38-gauge subretinal cannula, and the RPE strips were injected into the retinal bleb using a 31-gauge cannula with the maximum graft dose limited to 2 strips. Main Outcome Measures: The reduction of RPE abnormal area by the engraftment of transplanted allogeneic iPSC-derived RPE cells, which was measured by analyzing fluorescein angiography with an automated evaluation program at pretransplantation and up to 52 weeks posttransplantation. Results: The primary endpoint of reducing abnormal areas of RPE through the survival of the transplanted graft cells was achieved in all patients at 52 weeks posttransplantation. Visual function assessments confirmed significant vision-related quality of life improvement and potential retinal sensitivity restoration in 1 patient with dry AMD. The successful subretinal delivery of the iPSC-derived RPE strips was confirmed during and immediately after surgery. The engraftment of RPE cells migrated out from the strips was observed using polarization-sensitive OCT specifically and visualized as characteristic hexagonal cells via adaptive optics imaging in all patients. While no serious adverse events occurred, suspected immune reactions to graft cells and epiretinal membrane formation were observed in 1 patient each. Conclusions: A decrease in the RPE abnormal area by reliable delivery of allogeneic iPSC-derived RPE strips was achieved in all 3 cases with no serious adverse events. Further long-term studies and larger cohorts with better preoperative vision are warranted to evaluate the safety and efficacy of RPE strip transplantation. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914525000685Age-related macular degenerationiPS cellsRetinal pigment epitheliumRetinitis pigmentosaRPE transplantation |
| spellingShingle | Daiki Sakai, MD Michiko Mandai, MD, PhD Yasuhiko Hirami, MD, PhD Midori Yamamoto, BA Shin-ichiro Ito, MD, PhD Saori Igarashi, MD Satoshi Yokota, MD, PhD Hirofumi Uyama, MD, PhD Masashi Fujihara, MD, PhD Akiko Maeda, MD, PhD Motoki Terada, BS Mitsuhiro Nishida, MS Yumiko Shibata, MS Naoko Hayashi, MS Kyoko Iseki, MA Takuya Miura, MS Keisuke Kajita, MD, PhD Masaaki Ishida, MD, PhD Sunao Sugita, MD, PhD Tadao Maeda, MD, PhD Masayo Takahashi, MD, PhD Yasuo Kurimoto, MD, PhD Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa Ophthalmology Science Age-related macular degeneration iPS cells Retinal pigment epithelium Retinitis pigmentosa RPE transplantation |
| title | Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa |
| title_full | Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa |
| title_fullStr | Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa |
| title_full_unstemmed | Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa |
| title_short | Transplant of Induced Pluripotent Stem Cell–Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa |
| title_sort | transplant of induced pluripotent stem cell derived retinal pigment epithelium strips for macular degeneration and retinitis pigmentosa |
| topic | Age-related macular degeneration iPS cells Retinal pigment epithelium Retinitis pigmentosa RPE transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S2666914525000685 |
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