Diabetes and Obesity Center, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA.
Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY, USA.
Sci Rep. 2020 Sep 8;10(1):14754. doi: 10.1038/s41598-020-71580-z.
Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration-suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably linked to wound healing/remodeling in the ischemically injured heart, the reparative actions of CMCs may be attributed to their immunoregulatory properties. The current study evaluated the consequences of CMC administration on post myocardial infarction (MI) immune responses in vivo and paracrine-mediated immune cell function in vitro. CMC administration preferentially elicited the recruitment of cell types associated with innate immunity (e.g., monocytes/macrophages and neutrophils). CMC paracrine signaling assays revealed enhancement in innate immune cell chemoattraction, survival, and phagocytosis, and diminished pro-inflammatory immune cell activation; data that identifies and catalogues fundamental immunomodulatory properties of CMCs, which have broad implications regarding the mechanism of action of CMCs in cardiac repair.
尽管心脏间质细胞 (CMC) 疗法可以减轻心肌梗死后的心脏功能障碍，但潜在的机制仍不清楚。人们承认供体细胞既没有明显保留，也没有对组织再生有意义的贡献——这表明存在旁分泌介导的作用机制。由于免疫系统与缺血性损伤心脏中的伤口愈合/重塑密不可分，因此 CMC 的修复作用可能归因于其免疫调节特性。本研究评估了 CMC 给药对心肌梗死后 (MI) 体内免疫反应和旁分泌介导的免疫细胞功能的影响。CMC 给药优先募集与固有免疫相关的细胞类型（例如单核细胞/巨噬细胞和中性粒细胞）。CMC 旁分泌信号转导测定显示，固有免疫细胞的趋化性、存活和吞噬作用增强，促炎免疫细胞的激活减少；这些数据确定并编目了 CMC 的基本免疫调节特性，这对 CMC 在心脏修复中的作用机制具有广泛的意义。
