S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury

Abstract

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.

S100A8 as a Promising Biomarker and Oncogenic Immune Protein in the Tumor Microenvironment: An Integrative Pancancer Analysis

“…S100A8 and S100A9 are members of the S100 calcium-binding protein family, and when these proteins combine (S100A8/A9), they create the physiologically relevant version known as calprotectin. S100A8/A9 is granulocyte- and monocyte-specific and is involved in various pathological processes, such as inflammation, infection, and autoimmune diseases [ 21 , 22 ]. S100A8/A9 proinflammatory action involves leukocyte recruitment, cytokine and chemokine secretion enhancement, and leukocyte adhesion and migration modulation [ 23 ].…”

Letter by Ren and Yang Regarding Article, “Retention of the NLRP3 Inflammasome–Primed Neutrophils in the Bone Marrow Is Essential for Myocardial Infarction–Induced Granulopoiesis”

“…Furthermore, S100A8/A9 enhances the therapeutic paracrine effects of human amniotic mesenchymal stem cells in aspects of anti-inflammation, antifibrosis, and cardiac function preservation after myocardial infarction. 5 It implies that intravenous administration of the conditioned medium of S100A8/A9-pretreated human amniotic mesenchymal stem cells improved left ventricular function and decreased myocardial fibrosis after ischemia/reperfusion injury. 5 After myocardial infarction, neutrophils rapidly infiltrate the infarcted heart and release various proteins, including S100A8/A9, which, in turn, initiate the NLRP3 inflammasome.…”

“…Furthermore, S100A8/A9 enhances the therapeutic paracrine effects of human amniotic mesenchymal stem cells in aspects of anti-inflammation, antifibrosis, and cardiac function preservation after myocardial infarction. 5…”

“…It implies that intravenous administration of the conditioned medium of S100A8/A9-pretreated human amniotic mesenchymal stem cells improved left ventricular function and decreased myocardial fibrosis after ischemia/reperfusion injury. 5 After myocardial infarction, neutrophils rapidly infiltrate the infarcted heart and release various proteins, including S100A8/A9, which, in turn, initiate the NLRP3 inflammasome. Because of the dual roles of S100A8/A9 in different cells and multiple functions in different cells, it seems prudent to investigate the ability of S100A8/A9 and the NLRP3 inflammasome to specifically improve cardiovascular disease outcomes.…”

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…Because of the paracrine effects promoting repair of mesenchymal stem cells (MSCs), preconditioned MSCs in situ may be promising for post-MI repair ( Sim et al, 2021 ). The paracrine therapeutic anti-inflammatory and antifibrotic effects of human amniotic MSCs are increased by S100A8/A9 and calcium-binding proteins after MI ( Chen et al, 2021c ). Moreover, subcutaneous implantation of TheraCyte devices encapsulating human W8B2+ cardiac stem cells improves cardiac remodeling and function after MI ( Kompa et al, 2021 ), and stem cells-derived CMs patches restore normal electrical propagation without the risk of arrhythmia ( Fassina et al, 2022 ).…”