Cortical Bone Stem Cells Modify Cardiac Inflammation After Myocardial Infarction By Inducing a Novel Macrophage Phenotype

Am J Physiol Heart Circ Physiol. 2021 Aug 20. doi: 10.1152/ajpheart.00304.2021. Online ahead of print.ABSTRACTAcute damage to the heart, as in the case of myocardial infarction (MI), triggers a robust inflammatory response to the sterile injury that is part of a complex and highly organized wound healing process. Cortical bone stem cell (CBSC) therapy after MI has been shown to reduce adverse structural and functional remodeling of the heart after MI in both mouse and swine models. The basis for these CBSC treatment effects on wound healing are unknown. The present experiments show that CBSCs secrete paracrine factors known to have immunomodulatory properties, most notably Macrophage Colony Stimulating Factor (M-CSF) and Transforming Growth Factor-b, but not IL-4. CBSC therapy increased the number of Galectin-3+ macrophages, CD4+ T-cells, and fibroblasts in the heart while decreasing apoptosis in an in vivo swine model of MI. Macrophages treated with CBSC medium in vitro polarized to a pro-reparative phenotype characterized by increased CD206 expression, increased efferocytic ability, increased IL-10, TGF-b, and IL-1RA secretion, and increased mitochondrial respiration. Next generation sequencing revealed a transcriptome significantly different from M2a or M2c macrophage phenotypes. Paracrine factors from CBSC-treated macrophages increased proliferation, decreased a-Smooth Muscle Actin expression, and decreased contraction by fibroblasts in vitro. These data support the idea ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research