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Cardiomyocyte membrane breakdown in patients with DMD yields a serum injury profile similar to other types of myocardial injury with the release of creatine kinase and troponin isoforms. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly useful but can be improved. We generated hiPSC-CMs from a patient with DMD and subjected these cells to equibiaxial mechanical strain to mimic in vivo stress. Compared to healthy cells, DMD hiPSC-CMs demonstrated greater susceptibility to equibiaxial strain after 2\u2005h at 10% strain. We generated an aptamer-based profile of proteins released from hiPSC-CMs both at rest and subjected to strain and identified a strong correlation in the mechanical stress-induced proteome from hiPSC-CMs and serum from patients with DMD. We exposed hiPSC-CMs to recombinant annexin A6, a protein resealing agent, and found reduced biomarker release in DMD and control hiPSC-CMs subjected to strain. Thus, the application of mechanical strain to hiPSC-CMs produces a model that reflects an in vivo injury profile, providing a platform to assess pharmacologic intervention.<\/jats:p>","DOI":"10.1242\/dmm.050487","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T09:16:07Z","timestamp":1701767767000},"source":"Crossref","is-referenced-by-count":6,"title":["Physiological stress improves stem cell modeling of dystrophic cardiomyopathy"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7627-7119","authenticated-orcid":false,"given":"Dominic E.","family":"Fullenkamp","sequence":"first","affiliation":[{"name":"Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University 1 , Chicago, IL 60611 , USA"},{"name":"Feinberg School of Medicine, Northwestern University 2 Division of Cardiology, Department of Medicine , , Chicago, IL 60611 , 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T.","family":"Dittloff","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago 3 Department of Physiology and Biophysics , , Chicago, IL 60612 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sloane I.","family":"Harris","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University 1 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana A.","family":"Chychula","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University 1 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory W.","family":"Holgren","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University 1 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-0006","authenticated-orcid":false,"given":"Paul W.","family":"Burridge","sequence":"additional","affiliation":[{"name":"Northwestern University 4 Department of Pharmacology, Feinberg School of Medicine , , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-5836","authenticated-orcid":false,"given":"Brenda","family":"Russell","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago 3 Department of Physiology and Biophysics , , Chicago, IL 60612 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-125X","authenticated-orcid":false,"given":"Alexis R.","family":"Demonbreun","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University 1 , Chicago, IL 60611 , 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