Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.

Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.
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人类沃顿商学院果冻源间充质干细胞治疗视网膜变性的安全性和有效性。

DOI:
10.1371/journal.pone.0128973
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Then KY
Then KY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Leow SN;Luu CD;Hairul Nizam MH;Mok PL;Ruhaslizan R;Wong HS;Wan Abdul Halim WH;Ng MH;Ruszymah BH;Chowdhury SR;Bastion ML;Then KY

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探讨视网膜下注射人华顿氏胶源性间充质干细胞(hWJ-MSCs)对皇家外科学院(RCS)大鼠视网膜结构和功能的影响。RCS大鼠分为2组:hWJ-MSCs治疗组(n = 8)和安慰剂对照组(n = 8)。在治疗组中,在第21天,将来自健康供体的hWJ-MSC注射到每只大鼠的一只眼睛的视网膜下腔中。对照组注射等量生理盐水。另外3只动物注射纳米金标记的干细胞,用于使用微型计算机断层扫描(microCT)体内追踪细胞定位。在注射前3天通过视网膜电图(ERG)评估视网膜功能,并在注射后15、30和70天重复。在第70天收集眼睛用于组织学、细胞和分子研究。在研究期间,通过组织学未检测到视网膜肿瘤形成。MicroCT扫描显示,hWJ-MSC停留在眼睛中,没有全身迁移。透射电子显微镜显示,纳米金标记的细胞位于视网膜下腔。组织学显示治疗组保留了外核层(ONL),但对照组未保留。然而,两组之间的ERG反应没有显著差异。共聚焦显微镜显示hWJ-MSCs表达感光细胞、Müller细胞和双极细胞标记物的证据。视网膜下注射hWJ-MSC延迟RCS大鼠中ONL的丢失。hWJ-MSCs似乎是安全的,并具有分化为视网膜样细胞的潜力。这种基于细胞的治疗视网膜营养不良的潜力值得进一步研究。
To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.
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