Key result
Human epicardium-derived cells produce human collagen type I within 48 hours of transplantation into infarcted mouse hearts, and in vitro cyclic straining significantly induces collagen type I expression via the TGFβ/ALK5 signaling pathway.
Why the study?
It was unknown whether human epicardium-derived cells contribute to preservation of cardiac function after myocardial infarction via secretion of matrix proteins or matrix proteases to reduce scar formation.
Does transplantation of hEPDCs and exposure to cyclic strain induce collagen type I production and matrix remodeling in the post-MI environment?
Does transplantation of hEPDCs and exposure to cyclic strain induce collagen type I production and matrix remodeling in the post-MI environment?
Human epicardium-derived cells can synthesize their own extracellular matrix, specifically collagen type I, in response to mechanical strain and TGF-β signaling, providing insight into their mechanisms of cardiac repair post-myocardial infarction.
hEPDC collagen secretion may limit post-MI scarring; leaves open translation to human cell therapy.
Human epicardium-derived cells (hEPDCs) transplanted in the NOD-SCID mouse heart after myocardial infarction (MI) are known to improve cardiac function, most likely orchestrated by paracrine mechanisms that limit adverse remodeling. It is not yet known, however, if hEPDCs contribute to preservation of cardiac function via the secretion of matrix proteins and/or matrix proteases to reduce scar formation. This study describes the ability of hEPDCs to produce human collagen type I after transplantation into the infarct border zone, thereby creating their own extracellular environment. As the in vivo environment is too complex to investigate the mechanisms involved, we use an in vitro set-up, mimicking biophysical and biochemical cues from the myocardial tissue to unravel hEPDC-induced matrix remodeling. The in vivo contribution of hEPDCs to the cardiac extracellular matrix (ECM) was assessed in a historical dataset of the NOD-SCID murine model of experimentally induced MI and cell transplantation. Analysis showed that within 48 hours after transplantation, hEPDCs produce human collagen type I. The build-up of the human collagen microenvironment was reversed within 6 weeks. To understand the hEPDCs response to the pathologic cardiac microenvironment, we studied the influence of cyclic straining and/or transforming growth beta (TGFβ) signaling in vitro. We revealed that 48 hours of cyclic straining induced collagen type I production via the TGFβ/ALK5 signaling pathway. The in vitro approach enables further unraveling of the hEPDCs ability to secrete matrix proteins and matrix proteases and the potential to create and remodel the cardiac matrix in response to injury.
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Bax et al. (2019) studied Myocardial infarction (experimental model) (n=5). Human epicardium-derived cells (hEPDCs) transplantation and cyclic straining vs. Static culture (in vitro) was evaluated on Expression of collagen type I. Human epicardium-derived cells produce human collagen type I within 48 hours of transplantation into infarcted mouse hearts, and in vitro cyclic straining significantly induces collagen type I expression via the TGFβ/ALK5 signaling pathway.
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