CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect.
CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect.
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DOI：
10.1172/jci.insight.89906
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发表时间：
2017-01
期刊：
影响因子：
8
通讯作者：
S. Sakimoto;Valentina Marchetti;E. Aguilar;Kelsey Lee;Y. Usui;Salome Murinello;Felicitas Bucher;Jennifer K Trombley;Regis Fallon;R. Wagey;C. Peters;Elizabeth L. Scheppke;P. Westenskow;M. Friedlander
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作者：
S. Sakimoto;Valentina Marchetti;E. Aguilar;Kelsey Lee;Y. Usui;Salome Murinello;Felicitas Bucher;Jennifer K Trombley;Regis Fallon;R. Wagey;C. Peters;Elizabeth L. Scheppke;P. Westenskow;M. Friedlander
血管异常是眼科疾病的常见组成部分，通常会导致视力丧失。血管闭塞与遗传性视网膜变性有关，因为光感受器萎缩降低了局部代谢需求，不再需要对这些区域的血管支持。鉴于视网膜中神经血管的串扰程度，在面临严重压力时，使用一种细胞类型来挽救另一种细胞类型是可能的，例如缺氧或遗传编码的细胞特异性退化。在这里，我们展示了玻璃体内注射人内皮细胞集落形成细胞(ECFC)，这种细胞可以在无异种介质中从脐带血中分离和分化，收集在玻璃体腔内，挽救视网膜疾病动物模型中的血管闭塞和神经变性。此外，我们确定ECFC的一部分在解剖学和功能上预防视网膜病变更有效；这些细胞表达高水平的CD44，透明质酸受体和IGFBPs(胰岛素样生长因子结合蛋白)。注射ECFCs培养液或仅注射重组人IGFBPs也可挽救缺血表型。这些结果有助于我们理解基于ECFC的治疗缺血性损伤和视网膜神经退行性疾病的机制。
Vascular abnormalities are a common component of eye diseases that often lead to vision loss. Vaso-obliteration is associated with inherited retinal degenerations, since photoreceptor atrophy lowers local metabolic demands and vascular support to those regions is no longer required. Given the degree of neurovascular crosstalk in the retina, it may be possible to use one cell type to rescue another cell type in the face of severe stress, such as hypoxia or genetically encoded cell-specific degenerations. Here, we show that intravitreally injected human endothelial colony-forming cells (ECFCs) that can be isolated and differentiated from cord blood in xeno-free media collect in the vitreous cavity and rescue vaso-obliteration and neurodegeneration in animal models of retinal disease. Furthermore, we determined that a subset of the ECFCs was more effective at anatomically and functionally preventing retinopathy; these cells expressed high levels of CD44, the hyaluronic acid receptor, and IGFBPs (insulin-like growth factor-binding proteins). Injection of cultured media from ECFCs or only recombinant human IGFBPs also rescued the ischemia phenotype. These results help us to understand the mechanism of ECFC-based therapies for ischemic insults and retinal neurodegenerative diseases.