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成人牙周韧带干细胞延缓 RCS 大鼠的视网膜变性并维持其视网膜功能。

Adult human periodontal ligament-derived stem cells delay retinal degeneration and maintain retinal function in RCS rats.

机构信息

Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310003, China.

出版信息

Stem Cell Res Ther. 2017 Dec 22;8(1):290. doi: 10.1186/s13287-017-0731-y.

DOI:10.1186/s13287-017-0731-y
PMID:29273085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5741902/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

视网膜变性(RD)是导致全球数百万人失明的主要原因。干细胞移植被认为是治疗视网膜退行性疾病的一种有前途的方法。本研究旨在探讨人牙周膜干细胞(hPDLSCs)移植治疗 RCS 大鼠视网膜变性的治疗潜力。

方法

将 hPDLSCs 注射到 3 周龄 RCS 大鼠的视网膜下腔。对照组接受磷酸盐缓冲液注射或未处理。通过视网膜电图记录评估视网膜功能。之后收集眼睛进行组织学和分子研究。

结果

在 hPDLSC 移植后 2 周观察到维持视网膜功能,并持续至 8 周。在移植后 4 周和 8 周,hPDLSC 移植眼的视网膜结构得到保存,表现为外核层厚度的保存和 Rho、Crx 和视蛋白基因的表达。与对照组相比,hPDLSC 注射视网膜中末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记阳性凋亡光感受器的百分比显著降低。还发现 hPDLSCs 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、神经营养素-3、胰岛素样生长因子 1、神经生长因子和胶质细胞系源性神经营养因子。

结论

我们的研究结果表明,hPDLSC 移植可有效延缓光感受器丧失,并显著保存 RCS 大鼠的视网膜功能。这项研究支持进一步探索 hPDLSCs 治疗 RD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/006eced5da15/13287_2017_731_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/20d8bd3bfccc/13287_2017_731_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/fac9e30c22a4/13287_2017_731_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/9fe8a70de0a7/13287_2017_731_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/1b8fcbfd61df/13287_2017_731_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/006eced5da15/13287_2017_731_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/20d8bd3bfccc/13287_2017_731_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/c1060798b20c/13287_2017_731_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/3d0be49d3824/13287_2017_731_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/6eba1614c304/13287_2017_731_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/fac9e30c22a4/13287_2017_731_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/9fe8a70de0a7/13287_2017_731_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/1b8fcbfd61df/13287_2017_731_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c60/5741902/006eced5da15/13287_2017_731_Fig8_HTML.jpg

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