Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing.
Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing.
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DOI：
10.1167/iovs.18-24803
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Djalilian AR
中科院分区：
文献类型：
--
作者：
Samaeekia R;Rabiee B;Putra I;Shen X;Park YJ;Hematti P;Eslani M;Djalilian AR
间充质基质细胞（MSC）已被用于治疗调节炎症和促进修复。细胞外囊泡，包括外来体，已被确定为重要的介质之一。本研究探讨了人角膜MSC来源的外泌体对角膜上皮伤口愈合的影响。从人尸体角膜分离角膜MSC（cMSC）。在72小时后收集分泌体，并使用差示超离心分离外来体。通过电子显微镜和动态光散射检测外泌体的形态和大小。通过蛋白质印迹法评估cMSC外来体的⑶ 9、⑶ 63和⑶ 81的表达。使用钙黄绿素染色的外来体研究外来体的细胞摄取。使用划痕测定法在体外测量外泌体对伤口愈合的影响，并在小鼠中2-mm上皮清创伤口后在体内测量外泌体对伤口愈合的影响。cMSC外泌体在形态上是圆形的，并且主要群体的直径在40和100 nm之间。它们表达CD 9、CD 63和CD 81，不表达GM 130、钙连接蛋白和细胞色素C。染色的cMSC外泌体在体外被人cMSC、人角膜上皮细胞（HCEC）和人巨噬细胞以及在体内被角膜上皮成功摄取。在划痕试验中，16小时后，与对照中的72.9% ± 8%相比，cMSC外来体处理的HCEC具有30.1% ± 14%的剩余伤口面积（P < 0.005）。在体内，72小时后，与对照组中的41.6% ± 7%相比，cMSC外泌体处理的角膜具有77.5% ± 3%的角膜伤口愈合（P < 0.05）。人cMSC外泌体可以加速角膜上皮伤口愈合，因此可以为眼表损伤提供治疗方法。
Mesenchymal stromal cells (MSCs) have been used therapeutically to modulate inflammation and promote repair. Extracellular vesicles, including exosomes, have been identified as one of the important mediators. This study investigated the effect of human corneal MSC-derived exosomes on corneal epithelial wound healing. Corneal MSCs (cMSCs) were isolated from human cadaver corneas. The secretome was collected after 72 hours and exosomes were isolated using differential ultracentrifugation. Morphology and size of exosomes were examined by electron microscopy and dynamic light scattering. Expression of CD9, CD63, and CD81 by cMSC exosomes was evaluated by western blotting. Cellular uptake of exosomes was studied using calcein-stained exosomes. The effect of exosome on wound healing was measured in vitro using a scratch assay and in vivo after 2-mm epithelial debridement wounds in mice. cMSC exosomes were morphologically round and main population ranged between 40 and 100 nm in diameter. They expressed CD9, CD63, and CD81, and did not express GM130, Calnexin, and Cytochrome-C. Stained cMSC exosomes were successfully taken up by human cMSCs, human corneal epithelial cells (HCECs), and human macrophages in vitro and by corneal epithelium in vivo. In scratch assay, after 16 hours, cMSC exosome treated HCECs had 30.1% ± 14% remaining wound area compared to 72.9% ± 8% in control (P < 0.005). In vivo, after 72 hours, cMSC exosome-treated corneas had 77.5% ± 3% corneal wound healing compared to 41.6% ± 7% in the control group (P < 0.05). Human cMSC exosomes can accelerate corneal epithelial wound healing, and thus, may provide a therapeutic approach for ocular surface injuries.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
DOI：
10.1002/stem.2781
发表时间：
2018-05
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Eslani M;Putra I;Shen X;Hamouie J;Tadepalli A;Anwar KN;Kink JA;Ghassemi S;Agnihotri G;Reshetylo S;Mashaghi A;Dana R;Hematti P;Djalilian AR
通讯作者：
Djalilian AR
间充质干细胞衍生的外泌体作为肝病的新治疗策略。
影响因子：
12.8
作者：
Lou G;Chen Z;Zheng M;Liu Y
通讯作者：
Liu Y
影响因子：
4.1
作者：
Li, Fei;Zhao, Shao-Zhen
通讯作者：
Zhao, Shao-Zhen
影响因子：
3.4
作者：
Cejkova, Jitka;Trosan, Peter;Holan, Vladimir
通讯作者：
Holan, Vladimir