Transplantation of human induced pluripotent stem cell-derived neural crest cells for corneal endothelial regeneration.
Transplantation of human induced pluripotent stem cell-derived neural crest cells for corneal endothelial regeneration.
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移植人诱导多能干细胞源性神经嵴细胞用于角膜内皮再生
DOI：
10.1186/s13287-021-02267-z
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发表时间：
2021-03-29
影响因子：
7.5
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Gong Y;Duan H;Wang X;Zhao C;Li W;Dong C;Li Z;Zhou Q
角膜内皮通过屏障和泵功能维持角膜的水化，其功能障碍可引起角膜水肿和视力下降。考虑到它的发展从神经嵴细胞（NCCs），在这里，我们研究了人诱导的多能干细胞（hiPSC）衍生的NCCs的角膜内皮再生的功效在rabbit.Methodsdirected分化的hiPSC衍生的NCCs实现使用化学成分确定的培养基含有GSK-3抑制剂和TGF-β抑制剂。通过免疫荧光染色、流式细胞仪分析和体外多谱系分化能力对分化的细胞进行表征。对于体内功能评价，在去除角膜内皮后，将1.0 × 106 hiPSC衍生的NCC或NIH-3 T3成纤维细胞（作为对照）与100 μM Y-27632组合前房内注射到兔的前房中。兔角膜厚度和移植细胞的表型变化进行了检查，在7和14天，方便的厚度计，双免疫荧光染色，和定量RT-PCR.ResultsThe hiPSC衍生的NCCs分化均匀，通过7天的诱导，并表现出多谱系分化能力，外周神经元，间充质干细胞，角膜基质细胞。在兔中前房内注射7天后，与注射成纤维细胞的对照兔相比，hiPSC衍生的NCC导致正常角膜厚度和透明度的逐渐恢复。然而，14天后的恢复效果恶化，并导致角膜水肿的再次出现。机械地，移植的细胞表现出受损的成熟，细胞衰老，和内皮间质转化（EnMT）后的早期阶段的体内定向differentiation.ConclusionsTransplantation的hiPSC衍生的NCCs迅速恢复兔角膜厚度和清晰度。然而，移植细胞的不适当的成熟、衰老和EnMT损害了长期恢复功效。
BackgroundThe corneal endothelium maintains corneal hydration through the barrier and pump function, while its dysfunction may cause corneal edema and vision reduction. Considering its development from neural crest cells (NCCs), here we investigated the efficacy of the human induced pluripotent stem cell (hiPSC)-derived NCCs for corneal endothelial regeneration in rabbits.MethodsDirected differentiation of hiPSC-derived NCCs was achieved using the chemically defined medium containing GSK-3 inhibitor and TGF-β inhibitor. The differentiated cells were characterized by immunofluorescence staining, FACS analysis, and in vitro multi-lineage differentiation capacity. For in vivo functional evaluation, 1.0 × 106hiPSC-derived NCCs or NIH-3 T3 fibroblasts (as control) combined with 100 μM Y-27632 were intracamerally injected into the anterior chamber of rabbits following removal of corneal endothelium. Rabbit corneal thickness and phenotype changes of the transplanted cells were examined at 7 and 14 days with handy pachymeter, dual-immunofluorescence staining, and quantitative RT-PCR.ResultsThe hiPSC-derived NCCs were differentiated homogenously through 7 days of induction and exhibited multi-lineage differentiation capacity into peripheral neurons, mesenchymal stem cells, and corneal keratocytes. After 7 days of intracameral injection in rabbit, the hiPSC-derived NCCs led to a gradual recovery of normal corneal thickness and clarity, when comparing to control rabbit with fibroblasts injection. However, the recovery efficacy after 14 days deteriorated and caused the reappearance of corneal edema. Mechanistically, the transplanted cells exhibited the impaired maturation, cellular senescence, and endothelial-mesenchymal transition (EnMT) after the early stage of the in vivo directional differentiation.ConclusionsTransplantation of the hiPSC-derived NCCs rapidly restored rabbit corneal thickness and clarity. However, the long-term recovery efficacy was impaired by the improper maturation, senescence, and EnMT of the transplanted cells.
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影响因子：
4.4
作者：
Bartakova A;Alvarez-Delfin K;Weisman AD;Salero E;Raffa GA;Merkhofer RM Jr;Kunzevitzky NJ;Goldberg JL
通讯作者：
Goldberg JL
影响因子：
6
作者：
Inagaki E;Hatou S;Higa K;Yoshida S;Shibata S;Okano H;Tsubota K;Shimmura S
通讯作者：
Shimmura S
影响因子：
3.4
作者：
Matthaei, Mario;Zhu, Angela Y.;Kallay, Laura;Eberhart, Charles G.;Cursiefen, Claus;Jun, Albert S.
通讯作者：
Jun, Albert S.
影响因子：
4.4
作者：
Song JS;Lee JG;Kay EP
通讯作者：
Kay EP
在慢性角膜同种异体移植失败中，TGF-β 通过增加线粒体活性氧来诱导角膜内皮衰老。
DOI：
10.18632/aging.101659
发表时间：
2018-11-28
期刊：
Aging
影响因子：
--
作者：
Li Z;Liu T;Ma J;Guo Q;Ma L;Lv Q;Jiang Y;Wei C;Zhang J
通讯作者：
Zhang J