da Cruz Lyndon, Soomro Taha, Georgiadis Odysseas, Nommiste Britta, Sagoo Mandeep S, Coffey Peter
The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK.
National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK.
Diagnostics (Basel). 2024 May 13;14(10):1005. doi: 10.3390/diagnostics14101005.
(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)-the patch-and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject.
（1）背景：我们评估了一种针对晚期新生血管性年龄相关性黄斑变性（nAMD）的干细胞衍生治疗策略，该策略使用在包被的合成基底膜（BM）——贴片上递送的人胚胎干细胞衍生视网膜色素上皮（hESC-RPE）单层细胞，并评估了移植后5年hESC-RPE的存在和分布情况以及功能结局。（2）方法：两名因晚期nAMD黄斑下出血导致急性视力丧失的受试者接受了hESC-RPE贴片治疗。围手术期采用系统性免疫抑制，随后进行局部长效免疫抑制。对受试者进行了5年的监测，观察RPE贴片色素沉着情况、其超出贴片边界延伸至周围视网膜的情况、hESC-RPE和合成BM的厚度，并评估hESC-RPE的迁移和增殖情况。还评估了视觉功能。（3）结果：两名研究参与者在5年期间均显示出贴片具有清晰的RPE特征，保留了一些视网膜超微结构，光学相干断层扫描显示有重塑、纤维化和变薄的迹象。对于两名参与者，均有证据表明色素在术后12个月内持续超出贴片边界延伸，之后稳定下来并一直保持到术后5年。两例患者hESC-RPE和BM厚度随时间的测量结果与这两层的预定义组织学测量结果一致。在任何一例中，均未发现单层细胞外有远处RPE迁移或增殖的证据。两名受试者的视力在2年内均有持续改善，其中一名受试者在5年内维持了改善。与基线相比，两名受试者在第1年时注视和微视野检查均有初步改善，不过干预后4年时只有一名受试者维持了这种改善。（4）结论：hESC-RPE贴片显示出持续色素沉着的证据，色素会延伸，在植入后长达5年覆盖裸露的宿主基底膜。有证据表明，这代表了贴片上以及宿主RPE缺失的贴片边界处的功能性RPE。hESC-RPE和BM厚度的测量结果表明这两层在5年后仍然存在。对于RPE迁移、增殖或肿瘤形成的假设风险，未引发安全担忧。一名受试者的视觉功能持续改善了2年，另一名受试者持续改善了5年。
