Adult human periodontal ligament-derived stem cells delay retinal degeneration and maintain retinal function in RCS rats.
Adult human periodontal ligament-derived stem cells delay retinal degeneration and maintain retinal function in RCS rats.
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成人牙周膜来源的干细胞延缓 RCS 大鼠视网膜变性并维持视网膜功能
DOI：
10.1186/s13287-017-0731-y
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发表时间：
2017-12-22
影响因子：
7.5
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Huang L;Li Z;Tian H;Wang W;Cui D;Zhou Z;Chen X;Cheung HS;Xu GT;Chen Y
视网膜变性（RD）是导致不可逆失明的主要原因，影响着全世界数百万人。干细胞移植被认为是治疗视网膜退行性疾病的一种很有前途的方法。本研究旨在探讨人类牙周韧带源性干细胞（hPDLSCs）在英国皇家学院外科医生（RCS）大鼠牙周韧带变性过程中的治疗潜力。将hPDLSCs注入3周龄RCS大鼠视网膜下间隙。对照动物接受磷酸盐缓冲盐水注射或未经治疗。视网膜电图记录评估视网膜功能。术后取眼进行组织学和分子学研究。在hPDLSC移植后2周观察到视网膜功能维持，并持续长达8周。在移植后4周和8周，hpdlsc移植眼的视网膜结构得以保存，这反映在外核层厚度和Rho、Crx和Opsin基因表达的保存上。注射hpdlsc的视网膜中末端脱氧核苷酸转移酶介导的dUTP镍端标记阳性凋亡光感受器的百分比明显低于对照组。hPDLSCs还表达多种神经营养因子，包括血管内皮生长因子、生物活性碱性成纤维细胞生长因子、脑源性神经营养因子、神经营养因子-3、胰岛素样生长因子1、神经生长因子和胶质细胞系来源的神经营养因子。我们的研究结果表明，hPDLSC移植可以有效延缓RCS大鼠的光感受器丧失，并显著保护视网膜功能。本研究支持进一步探索hPDLSCs治疗RD。本文的在线版本（doi:10.1186/s13287-017-0731-y）包含补充材料，可向授权用户提供。
Retinal degeneration (RD) is a leading cause of irreversible blindness, affecting millions of people worldwide. Stem cell transplantation has been considered a promising therapy for retinal degenerative diseases. This study aimed to investigate the therapeutic potential of human periodontal ligament-derived stem cells (hPDLSCs) for intervention in the progress of this degeneration in the Royal College Surgeons (RCS) rat. hPDLSCs were injected into the subretinal space of 3-week-old RCS rats. Control animals received a phosphate-buffered saline injection or were untreated. Retinal function was assessed by electroretinography recording. Eyes were collected afterward for histology and molecular studies. Retinal function maintenance was observed at 2 weeks and persisted for up to 8 weeks following hPDLSC transplantation. Retinal structure preservation was demonstrated in hPDLSC-transplanted eyes at 4 and 8 weeks following transplantation, as reflected in the preservation of outer nuclear layer thickness and gene expression of Rho, Crx, and Opsin. The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic photoreceptors was significantly lower in the hPDLSC-injected retinas than in those of the control groups. hPDLSCs were also found to express multiple neurotrophic factors, including vascular endothelial growth factor, bioactive basic fibroblast growth factor, brain-derived neurotrophic factor, neurotrophin-3, insulin-like growth factor 1, nerve growth factor, and glial cell line-derived neurotrophic factor. Our findings suggest that hPDLSC transplantation is effective in delaying photoreceptor loss and provides significant preservation of retinal function in RCS rats. This study supports further exploration of hPDLSCs for treating RD. The online version of this article (doi:10.1186/s13287-017-0731-y) contains supplementary material, which is available to authorized users.
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作者：
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通讯作者：
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