Transplantation of human pluripotent stem cell-derived retinal sheet in a primate model of macular hole.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-03 DOI:10.1016/j.stemcr.2024.09.002

Yasuaki Iwama, Yasuko Sugase-Miyamoto, Kenta Onoue, Hirofumi Uyama, Keiji Matsuda, Kazuko Hayashi, Ryutaro Akiba, Tomohiro Masuda, Satoshi Yokota, Shigenobu Yonemura, Kohji Nishida, Masayo Takahashi, Yasuo Kurimoto, Michiko Mandai

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Abstract

Macular hole (MH) is a retinal break involving the fovea that causes impaired vision. Although advances in vitreoretinal surgical techniques achieve >90% MH closure rate, refractory cases still exist. For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting. Here, using a non-human primate model, we evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating MH. After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed. Mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft. Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment.

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在灵长类动物黄斑孔模型中移植人类多能干细胞衍生视网膜片。

黄斑孔（MH）是一种涉及眼窝的视网膜破损，会导致视力受损。虽然玻璃体视网膜手术技术的进步使黄斑裂孔的闭合率达到90%以上，但难治性病例仍然存在。对于这类病例，自体视网膜移植是一种可选的治疗方法，在解剖学上取得了良好的效果，但视觉改善有限，移植后周边视野缺损不可避免。在此，我们利用非人灵长类动物模型，评估了人类胚胎干细胞衍生的视网膜类器官（RO）片移植是否是治疗MH的有效选择。移植后，通过用RO片连续填充MH空间，成功封闭了MH，从而改善了视觉功能，尽管没有证实宿主-移植突触连接。额外的局灶性类固醇注射控制了轻微的异种移植排斥反应，并且移植体中发育出了杆状/锥状光感受器。总之，我们的研究结果表明，多能干细胞衍生的RO片移植是治疗难治性MH的一种实用选择。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.