Developmental lineage of human pluripotent stem cell-derived cardiac fibroblasts affects their functional phenotype.

Autor: Floy ME; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA., Givens SE; Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA., Matthys OB; UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkley, CA, USA.; Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA., Mateyka TD; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA., Kerr CM; Molecular Cell Biology and Pathobiology Program, Medical University of South Carolina, Charleston, SC, USA., Steinberg AB; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA., Silva AC; Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA., Zhang J; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA., Mei Y; Department of Bioengineering, Clemson University, Clemson, SC, USA., Ogle BM; Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA., McDevitt TC; Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA., Kamp TJ; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA., Palecek SP; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Sep; Vol. 35 (9), pp. e21799.
DOI: 10.1096/fj.202100523R
Abstrakt: Cardiac fibroblasts (CFBs) support heart function by secreting extracellular matrix (ECM) and paracrine factors, respond to stress associated with injury and disease, and therefore are an increasingly important therapeutic target. We describe how developmental lineage of human pluripotent stem cell-derived CFBs, epicardial (EpiC-FB), and second heart field (SHF-FB) impacts transcriptional and functional properties. Both EpiC-FBs and SHF-FBs exhibited CFB transcriptional programs and improved calcium handling in human pluripotent stem cell-derived cardiac tissues. We identified differences including in composition of ECM synthesized, secretion of growth and differentiation factors, and myofibroblast activation potential, with EpiC-FBs exhibiting higher stress-induced activation potential akin to myofibroblasts and SHF-FBs demonstrating higher calcification and mineralization potential. These phenotypic differences suggest that EpiC-FBs have utility in modeling fibrotic diseases while SHF-FBs are a promising source of cells for regenerative therapies. This work directly contrasts regional and developmental specificity of CFBs and informs CFB in vitro model selection.
(© 2021 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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