The renal endothelium is a prime target for ischemia-reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regenerative effects of MSC on injured endothelial cells and to identify the molecular mechanisms involved. Human umbilical vein endothelial cells (HUVEC) were submitted to hypoxia and reoxygenation and TNF-α treatment. To determine whether physical interaction or soluble factors released by MSC were responsible for the potential regenerative effects of MSC on endothelial cells, dose-response experiments were performed in co-culture and transwell conditions and with secretome-deficient MSC. MSC showed increased migration and adhesion to injured HUVEC, mediated by CD29 and CD44 on the MSC membrane. MSC decreased membrane injury marker expression, oxidative stress levels, and monolayer permeability of injured HUVEC, which was observed only when allowing both physical and paracrine interaction between MSC and HUVEC. Furthermore, viable MSC in direct contact with injured HUVEC improved wound healing capacity by 45% and completely restored their angiogenic capacity. In addition, MSC exhibited an increased ability to migrate through an injured HUVEC monolayer compared to non-injured HUVEC in vitro. These results show that MSC have regenerative effects on injured HUVEC via a mechanism which requires both physical and paracrine interaction. The identification of specific effector molecules involved in MSC-HUVEC interaction will allow targeted modification of MSC to apply and enhance the therapeutic effects of MSC in IRI.

中文翻译：

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缺氧和炎性损伤后间充质基质细胞对内皮细胞的修复作用。

肾内皮是捐赠和移植过程中缺血再灌注损伤（IRI）的主要靶标。间充质基质细胞（MSC）已显示可改善IRI后的肾脏功能。但是，这是否涉及内皮的修复尚不清楚。因此，我们的目标是研究MSC对受损内皮细胞的潜在再生作用，并确定涉及的分子机制。人脐静脉内皮细胞（HUVEC）接受了缺氧和复氧以及TNF-α的治疗。为了确定MSC释放的物理相互作用或可溶性因子是否对MSC对内皮细胞的潜在再生作用负责，在共培养和穿孔条件下以及分泌蛋白缺乏的MSC中进行了剂量反应实验。MSC在MSC膜上的CD29和CD44介导的迁移和对受损HUVEC的粘附增加。MSC降低了受损HUVEC的膜损伤标志物表达，氧化应激水平和单层通透性，只有在MSC与HUVEC之间同时进行物理和旁分泌相互作用时，才能观察到这一点。此外，与受伤的HUVEC直接接触的可行MSC将伤口愈合能力提高了45％，并完全恢复了它们的血管生成能力。另外，与在体外未受伤的HUVEC相比，MSC表现出增加的通过受伤的HUVEC单层迁移的能力。这些结果表明，MSC通过需要物理和旁分泌相互作用的机制对受伤的HUVEC具有再生作用。