دورية أكاديمية
Transplantation of human induced pluripotent stem cell-derived neural crest cells for corneal endothelial regeneration
| العنوان: | Transplantation of human induced pluripotent stem cell-derived neural crest cells for corneal endothelial regeneration |
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| المؤلفون: | Yajie Gong, Haoyun Duan, Xin Wang, Can Zhao, Wenjing Li, Chunxiao Dong, Zongyi Li, Qingjun Zhou |
| المصدر: | Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine (General) LCC:Biochemistry |
| مصطلحات موضوعية: | iPSC, Neural crest cells, Corneal endothelium, Transplantation, Medicine (General), R5-920, Biochemistry, QD415-436 |
| الوصف: | Abstract Background The 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. Methods Directed 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 × 106 hiPSC-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. Results The 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. Conclusions Transplantation 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-6512 46878084 |
| Relation: | https://doaj.org/toc/1757-6512 |
| DOI: | 10.1186/s13287-021-02267-z |
| URL الوصول: | https://doaj.org/article/3cda536c4d7c4687808483ba57715741 |
| رقم الأكسشن: | edsdoj.3cda536c4d7c4687808483ba57715741 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17576512 46878084 |
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| DOI: | 10.1186/s13287-021-02267-z |