Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China.
Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
Adv Healthc Mater. 2022 Nov;11(22):e2200971. doi: 10.1002/adhm.202200971. Epub 2022 Sep 9.
Regulatory T cells overexpressing SPARC (secreted protein acidic and cysteine rich) (Sparc Tregs) can help repair infarct tissues after acute myocardial infarction (AMI). This research demonstrates that Sparc Treg-derived extracellular vesicles (EVs) effectively improved cardiac function through proinflammatory factors IL-1β, IL-6, and TNF-α inhibition and collagen synthesis related gene Col3a1 promotion in AMI; moreover, a composite hydrogel-EVs system (DHPM(4APPC)_EVs) is designed based on Sparc Treg-derived EVs with CXCR2 overexpressing and pH/H O /MMP9 temporally responsive gel microspheres. In AMI, due to the levels of chemokine, pH, H O , and MMP9 enzymes in the infarct area, DHPM(4APPC)_EVs can effectively target the infarct area, release the loaded EVs, form the gel to capture the released EVs, and slowly release the captured EVs, contribute to promote EVs to stay in the infarct area for a long time to play the repair function, so as to reduce myocardial injury and promote the improvement of cardiac function. The proposed system in this research provides a potential approach for the treatment of AMI in the future.
过表达富含半胱氨酸和酸性蛋白（secreted protein acidic and cysteine rich，SPARC）的调节性 T 细胞（Regulatory T cells overexpressing SPARC，Sparc Tregs）可帮助修复急性心肌梗死（acute myocardial infarction，AMI）后的梗死组织。本研究表明，Sparc Treg 衍生的细胞外囊泡（extracellular vesicles，EVs）通过抑制促炎因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）以及促进胶原合成相关基因 Col3a1 的表达，有效改善 AMI 后的心脏功能；此外，还设计了一种基于 Sparc Treg 衍生 EVs 的复合水凝胶-EVs 系统（DHPM(4APPC)_EVs），该系统具有过表达趋化因子受体 2（C-X-C 型配体受体 2，CXCR2）和对 pH/H 2 O 2 /基质金属蛋白酶 9（matrix metalloproteinase 9，MMP9）具有时间响应性的凝胶微球。在 AMI 中，由于梗死区域的趋化因子、pH 值、H 2 O 2 和 MMP9 酶的水平，DHPM(4APPC)_EVs 可有效靶向梗死区域，释放负载的 EVs，形成凝胶以捕获释放的 EVs，并缓慢释放捕获的 EVs，有助于促进 EVs 在梗死区域停留更长时间以发挥修复功能，从而减少心肌损伤并促进心脏功能的改善。本研究提出的系统为未来 AMI 的治疗提供了一种潜在的方法。
