Roy Sushmita, Spinali Keith, Schmuck Eric G, Kink John A, Hematti Peiman, Raval Amish N
Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Division of Hematology/Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
J Immunol Regen Med. 2020 Dec;10. doi: 10.1016/j.regen.2020.100033. Epub 2020 Oct 21.
The polarization of monocytes into macrophages that possess anti-inflammatory and pro-angiogenic properties could provide a novel therapeutic strategy for patients who are at a high risk for developing heart failure following myocardial infarction (MI). Here in, we describe a novel method of "educating" monocytes into a distinct population of macrophages that exhibit anti-inflammatory and pro-angiogenic features through a 3-day culture on fibronectin-rich cardiac matrix (CX) manufactured using cultured human cardiac fibroblasts. Our data suggest that CX can educate monocytes into a unique macrophage population termed CX educated macrophages (CXMq) that secrete high levels of VEGF and IL-6. , CXMq also demonstrate the ability to recruit mesenchymal stromal cells (MSC) with known anti-inflammatory properties. Selective inhibition of fibronectin binding to αVβ3 surface integrins on CXMq prevented MSC recruitment. This suggests that insoluble fibronectin within CX is, at least in part, responsible for CXMq conversion.
将单核细胞极化为具有抗炎和促血管生成特性的巨噬细胞，可能为心肌梗死（MI）后发生心力衰竭风险较高的患者提供一种新的治疗策略。在此，我们描述了一种将单核细胞“诱导”为独特巨噬细胞群体的新方法，该群体通过在使用培养的人心脏成纤维细胞制造的富含纤连蛋白的心脏基质（CX）上进行3天培养，表现出抗炎和促血管生成特性。我们的数据表明，CX可以将单核细胞诱导为一个独特的巨噬细胞群体，称为CX诱导巨噬细胞（CXMq），其分泌高水平的VEGF和IL-6。此外，CXMq还表现出招募具有已知抗炎特性的间充质基质细胞（MSC）的能力。对CXMq上纤连蛋白与αVβ3表面整合素结合的选择性抑制可阻止MSC的招募。这表明CX中不溶性纤连蛋白至少部分负责CXMq的转化。
