Inflammatory response regulation is a mechanism through which human umbilical cord mesenchymal stem cells (HUCMSCs) improve myocardial ischemia reperfusion injury (IRI); however, the timing of HUCMSC delivery to achieve maximum effectiveness is controversial. To investigate the effects of HUCMSC delivery on the acute inflammatory stage of IRI, we transplanted HUCMSCs or HUCMSCs with cyclosporin A (CsA) through the coronary artery simultaneously during ischemia reperfusion in pigs. Ferumoxytol-labeled HUCMSCs (HUCMSC), HUCMSCs with cyclosporin A (HUCMSC+CsA), and PBS (control) groups were investigated to evaluate the homing of transplanted cells and changes in infarct features, cardiac activity, and inflammatory response at three time points post-transplantation. Animals were sacrificed 2 weeks later for histological analysis of the hearts. We detected Prussian blue-dyed granules distributed around T lymphocyte clusters in the infarct area in the HUCMSC group. Infarct size and collagen deposition in the infarct area were lower in the HUCMSC group than in the control and HUCMSC+CsA groups. Cardiac function was mildly impaired in both the control and HUCMSC groups, whereas added CsA had a more severe impact. The levels of proinflammatory markers were lower in the HUCMSC group than in the control group at 24-h follow-up, and the difference was more significant after adding CsA. There were more CD3⁺ T lymphocytes and Foxp3⁺ Tregs in the HUCMSC group infarct area than in the other two groups. Proliferation rate of T lymphocytes was higher in the HUCMSC group than in the other two groups. Indirect co-culture experiments in vitro showed that MSCs promoted the generation of CD4⁺CD25⁺ Foxp3⁺Tregs through a paracrine mechanism. These results indicate that immediate intracoronary delivery of HUCMSCs after ischemia reperfusion can reduce acute myocardial IRI and promote myocardial repair, mainly through T lymphocyte interactions to regulate the intense inflammatory response during the acute inflammatory stage.

中文翻译：

---

人脐带间充质干细胞的立即冠状动脉内递送通过与 T 淋巴细胞的细胞间接触调节炎症过程来减少心肌损伤。

炎症反应调节是人脐带间充质干细胞（HUCMSCs）改善心肌缺血再灌注损伤（IRI）的机制；然而，HUCMSC 递送达到最大效果的时间是有争议的。为了研究 HUCMSCs 递送对 IRI 急性炎症阶段的影响，我们在猪缺血再灌注期间通过冠状动脉同时移植 HUCMSCs 或带有环孢菌素 A (CsA) 的 HUCMSCs。对 Ferumoxytol 标记的 HUCMSCs (HUCMSC)、带有环孢素 A (HUCMSC+CsA) 和 PBS（对照组）的 HUCMSCs 进行了研究，以评估移植细胞的归巢以及术后三个时间点的梗塞特征、心脏活动和炎症反应的变化-移植。2周后处死动物用于心脏的组织学分析。我们在 HUCMSC 组的梗塞区检测到分布在 T 淋巴细胞簇周围的普鲁士蓝染色颗粒。HUCMSC 组梗死面积和梗死区胶原沉积低于对照组和 HUCMSC+CsA 组。对照组和 HUCMSC 组的心脏功能均轻度受损，而添加 CsA 的影响更为严重。24 h随访时，HUCMSC组促炎标志物水平低于对照组，加入CsA后差异更显着。有更多的CD3 对照组和 HUCMSC 组的心脏功能均轻度受损，而添加 CsA 的影响更为严重。24 h随访时，HUCMSC组促炎标志物水平低于对照组，加入CsA后差异更显着。有更多的CD3 对照组和 HUCMSC 组的心脏功能均轻度受损，而添加 CsA 的影响更为严重。24 h随访时，HUCMSC组促炎标志物水平低于对照组，加入CsA后差异更显着。有更多的CD3HUCMSC组梗死区⁺ T淋巴细胞和Foxp3 ⁺ Tregs比其他两组多。HUCMSC组T淋巴细胞增殖率高于其他两组。体外间接共培养实验表明，MSCs通过旁分泌机制促进CD4 ⁺ CD25 ⁺ Foxp3 ⁺ Tregs的产生。这些结果表明，缺血再灌注后立即冠状动脉内递送 HUCMSCs 可以降低急性心肌 IRI 并促进心肌修复，主要通过 T 淋巴细胞相互作用来调节急性炎症阶段的强烈炎症反应。