Bone Marrow CD133(+) Stem Cells Ameliorate Visual Dysfunction in Streptozotocin-induced Diabetic Mice with Early Diabetic Retinopathy.
Bone Marrow CD133(+) Stem Cells Ameliorate Visual Dysfunction in Streptozotocin-induced Diabetic Mice with Early Diabetic Retinopathy.
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DOI：
10.1177/0963689718759463
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发表时间：
2018-06
影响因子：
3.3
通讯作者：
Yin ZQ
中科院分区：
文献类型：
--
作者：
Rong L;Gu X;Xie J;Zeng Y;Li Q;Chen S;Zou T;Xue L;Xu H;Yin ZQ
糖尿病视网膜病变 (DR) 是全世界视力丧失的主要原因之一，其特点是神经血管疾病。新的证据表明视网膜神经变性存在于 DR 的早期发病机制中，并且尚未开发出治疗方法来预防可检测到的微血管疾病之前的早期神经退行性变化。具有血运重建特性的骨髓 CD133+ 干细胞表现出神经再生潜力。然而，CD133+细胞是否可以改善DR早期的神经变性仍不清楚。在本研究中，通过免疫磁珠分离小鼠骨髓 CD133+ 干细胞，并分析其表型特征、神经分化能力和神经营养因子的基因表达。用增强型绿色荧光蛋白标记后，将 CD133+ 细胞玻璃体内移植到链脲佐菌素 (STZ) 诱导的糖尿病小鼠中，以评估视觉功能和视网膜结构的结果以及治疗效果的机制。我们发现CD133+细胞共表达典型的造血/内皮干/祖细胞表型，可以分化为神经谱系细胞，并在体外表达强大的神经营养因子的基因。功能分析表明，CD133+细胞移植可在 56 天内预防视觉功能障碍。组织学分析证实了这种功能改善，并显示移植的 CD133+ 细胞存活，随着时间的推移迁移到视网膜内层 (IR)，并保留了 IR 变性，包括视网膜神经节细胞 (RGC) 和杆状双极细胞。此外，神经节细胞层中移植的 CD133+ 细胞子集在 STZ 诱导的糖尿病视网膜中分化表达 RGC 标记。此外，移植的CD133+细胞在体内表达脑源性神经营养因子（BDNF），并增加STZ诱导的糖尿病视网膜中的BDNF水平，以支持视网膜细胞的存活。基于这些发现，我们认为骨髓 CD133+ 干细胞移植代表了一种改善 DR 早期视觉功能障碍和潜在 IR 神经变性的新方法。
Diabetic retinopathy (DR), one of the leading causes of vision loss worldwide, is characterized by neurovascular disorders. Emerging evidence has demonstrated retinal neurodegeneration in the early pathogenesis of DR, and no treatment has been developed to prevent the early neurodegenerative changes that precede detectable microvascular disorders. Bone marrow CD133+ stem cells with revascularization properties exhibit neuroregenerative potential. However, whether CD133+ cells can ameliorate the neurodegeneration at the early stage of DR remains unclear. In this study, mouse bone marrow CD133+ stem cells were immunomagnetically isolated and analyzed for the phenotypic characteristics, capacity for neural differentiation, and gene expression of neurotrophic factors. After being labeled with enhanced green fluorescent protein, CD133+ cells were intravitreally transplanted into streptozotocin (STZ)-induced diabetic mice to assess the outcomes of visual function and retina structure and the mechanism underlying the therapeutic effect. We found that CD133+ cells co-expressed typical hematopoietic/endothelial stem/progenitor phenotypes, could differentiate to neural lineage cells, and expressed genes of robust neurotrophic factors in vitro. Functional analysis demonstrated that the transplantation of CD133+ cells prevented visual dysfunction for 56 days. Histological analysis confirmed such a functional improvement and showed that transplanted CD133+ cells survived, migrated into the inner retina (IR) over time and preserved IR degeneration, including retina ganglion cells (RGCs) and rod-on bipolar cells. In addition, a subset of transplanted CD133+ cells in the ganglion cell layer differentiated to express RGC markers in STZ-induced diabetic retina. Moreover, transplanted CD133+ cells expressed brain-derived neurotrophic factors (BDNFs) in vivo and increased the BDNF level in STZ-induced diabetic retina to support the survival of retinal cells. Based on these findings, we suggest that transplantation of bone marrow CD133+ stem cells represents a novel approach to ameliorate visual dysfunction and the underlying IR neurodegeneration at the early stage of DR.
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影响因子：
20.1
作者：
Barcelos LS;Duplaa C;Kränkel N;Graiani G;Invernici G;Katare R;Siragusa M;Meloni M;Campesi I;Monica M;Simm A;Campagnolo P;Mangialardi G;Stevanato L;Alessandri G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
DOI：
10.1073/pnas.0710000105
发表时间：
2008-01-22
影响因子：
11.1
作者：
Coskun, Volkan;Wu, Hao;Sun, Yi E.
通讯作者：
Sun, Yi E.
影响因子：
7.5
作者：
Ezquer M;Urzua CA;Montecino S;Leal K;Conget P;Ezquer F
通讯作者：
Ezquer F
影响因子：
20.1
作者：
Friedrich, EB;Walenta, K;Werner, N
通讯作者：
Werner, N
影响因子：
5.3
作者：
Corti, Stefania;Nizzardo, Monica;Comi, Giacomo P.
通讯作者：
Comi, Giacomo P.