Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.
Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.
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DOI：
10.1371/journal.pone.0065691
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yates PA
中科院分区：
文献类型：
--
作者：
Mendel TA;Clabough EB;Kao DS;Demidova-Rice TN;Durham JT;Zotter BC;Seaman SA;Cronk SM;Rakoczy EP;Katz AJ;Herman IM;Peirce SM;Yates PA
视网膜血管病变，包括糖尿病视网膜病变(DR)，威胁着超过1亿人的视力。视网膜周细胞对微血管控制至关重要，通过直接接触和旁分泌机制支持视网膜内皮细胞。随着周细胞的死亡或丢失，内皮功能障碍接踵而至，导致缺氧性损伤、病理性血管生成，最终导致失明。脂肪来源的干细胞(ASCs)可以分化为周细胞，这表明它们可能对视网膜血管疾病的保护和再生细胞治疗有用。在这项研究中，我们研究了在多种视网膜血管病变的临床前模型中，ASCs分化为周细胞的能力，以稳定视网膜血管。我们发现ASCs在体外表达周细胞特异性标记。当将ASCs注射到氧源性视网膜病变(OIR)小鼠的玻璃体内时，ASCs能够迁移到视网膜血管系统并与之整合。整合的ASCs在体内保持标记表达和周细胞样形态至少2个月。在OIR血管失稳和消融后注射ASCs可促进血管再生(无血管面积减少16%)。在OIR血管失稳前玻璃体内注射ASCs可防止视网膜毛细血管脱落(减少53%)。转化生长因子-β(转化生长因子-β-1)处理的血管干细胞以与天然视网膜周细胞相似的方式增强血管内皮细胞周细胞的功能，在OIR中增加平滑肌肌动蛋白的标记物表达，细胞收缩，内皮稳定和微血管保护。最后，注射ASCs防止了糖尿病视网膜病变Akimba小鼠的毛细血管丢失(注射后2个月减少了79%)。ASC来源的周细胞可以与视网膜血管系统整合，采用周细胞形态和标志物表达，在多种视网膜血管病变模型中提供功能性血管保护。ASCs显示的周细胞表型在转化生长因子-β-1处理后增强，就像天然视网膜周细胞一样。ASCs可能代表了一种针对DR和其他视网膜血管疾病的保护和修复的创新细胞疗法。
Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs) differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR), ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction). Treatment of ASCs with transforming growth factor beta (TGF-β1) enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection). ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with TGF-β1 treatment, as seen with native retinal pericytes. ASCs may represent an innovative cellular therapy for protection against and repair of DR and other retinal vascular diseases.
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影响因子：
15.9
作者：
Jechlinger, Martin;Sommer, Andreas;Gruenert, Stefan
通讯作者：
Gruenert, Stefan
影响因子：
3.6
作者：
Chan, Rodney K.;Garfein, Evan;Orgill, Dennis P.
通讯作者：
Orgill, Dennis P.
DOI：
10.1007/s00417-007-0710-6
发表时间：
2008-02-01
影响因子：
2.7
作者：
Aoki, Hitomi;Hara, Akira;Kunisada, Takahiro
通讯作者：
Kunisada, Takahiro
影响因子：
6
作者：
Chan-Ling, T;Page, MP;Hughes, S
通讯作者：
Hughes, S
影响因子：
5.2
作者：
Katz, AJ;Tholpady, A;Ogle, RC
通讯作者：
Ogle, RC