Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose
Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose
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DOI：
10.1089/ten.tea.2019.0007
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发表时间：
2019-05-01
影响因子：
4.1
通讯作者：
Diaz Corrales, Francisco J.
中科院分区：
文献类型：
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作者：
Garcia Delgado, Ana B.;de la Cerda, Berta;Diaz Corrales, Francisco J.
老年性黄斑变性等疾病对视网膜色素上皮(RPE)的损伤会导致感光细胞死亡和失明。因此，人们正在探索RPE的替代疗法，以此作为治疗几种视网膜疾病的方法。为了走向未来个性化的自体移植方法，我们准备了一种生物相容的植入物，使用来自健康捐赠者单核细胞的诱导多能干细胞(IPSCs)重新编程的RPE。极化RPE的正确定位对于发挥其作用和保护光感受器免受退化是至关重要的。因此，我们使用了一种生物相容的纤维蛋白和琼脂糖凝胶基质，允许在视网膜下间隙手术放置RPE膜，保持其功能定位。我们的目的是在临床前模型中证明移植的安全性和可行性。猪被用来测试常规玻璃体视网膜手术的可行性。我们的结果表明，这种植入物适合于视网膜下移植，允许人RPE细胞存活并保持其表型和取向，而没有任何局部或全身不良反应。在视网膜退行性疾病的细胞治疗领域，一种新的生物材料被提出作为支架生长，并通过手术将单层视网膜色素上皮细胞引入视网膜下间隙，保持细胞的取向，以实现移植的适当功能整合。利用诱导多能干细胞作为视网膜色素上皮细胞的起始材料，旨在向个性化医学方法发展。
Damage to the retinal pigment epithelium (RPE) in age-related macular degeneration and other diseases results in photoreceptor cell death and blindness. Replacement of RPE is therefore being explored as a therapy for several retinal diseases. To move toward a future personalized autologous transplant approach, we have prepared a biocompatible implant using RPE derived from induced pluripotent stem cells (iPSCs) reprogrammed from a healthy donor's monocytes. The correct positioning of the polarized RPE is essential to fulfill its role and protect photoreceptors from degeneration. Hence, we have used a biocompatible hydrogel matrix of fibrin and agarose that allows the surgical placement of an RPE sheet in the subretinal space, keeping its functional orientation. Our aim was to demonstrate safety and viability of the transplant in preclinical models. Pigs were used to test the feasibility of a regular vitreoretinal surgery. Our results show that this implant is suitable for subretinal transplantation allowing human RPE cells to survive and maintain their phenotype and orientation without any local or systemic adverse events. The ability to transplant the iPSC-derived RPE sheet in its natural orientation will surely increase the chance to obtain a therapeutic effect in future translational studies.Impact Statement In the promising field of cellular therapy for retinal degenerative diseases, a new biomaterial is proposed as a scaffold to grow and surgically introduce a monolayer of retinal pigment epithelial cells into the subretinal space, keeping the orientation of the cells for a proper functional integration of the transplant. The use of induced pluripotent stem cells as the starting material for retinal pigment epithelial cells is intended to advance toward a personalized medicine approach.