{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:50Z","timestamp":1785430490548,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,15]]},"group-title":"Bioengineering","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01HL156947"],"award-info":[{"award-number":["R01HL156947"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL171205"],"award-info":[{"award-number":["R01HL171205"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["23TPA1058685"],"award-info":[{"award-number":["23TPA1058685"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Muscle LIM protein (MLP) is a critical regulator of cardiomyocytes (CMs) cytoarchitecture, and its deficiency results in late-onset dilated cardiomyopathy (DCM) in both mice and human. However, recapitulating this phenotype\n                  <jats:italic>in vitro<\/jats:italic>\n                  using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been challenging largely due to their immature state. Here, we generated MLP knockout (MLP-KO) mouse iPSCs and differentiated them into CMs. We then employed both conventional\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  transplantation approach using immunocompromised rat hearts to promote cardiomyocytes maturation. Our results showed that while\n                  <jats:italic>in vitro<\/jats:italic>\n                  -matured MLP-KO iPSC-CMs failed to exhibit disease phenotypes,\n                  <jats:italic>in vivo<\/jats:italic>\n                  -matured MLP-KO iPSC-CMs successfully recapitulated the hallmarks of DCM, including disrupted sarcomeric architecture and upregulation of atrial natriuretic peptide (ANP), closely mirroring disease progression observed in MLP-deficient mice. These findings demonstrate that the\n                  <jats:italic>in vivo<\/jats:italic>\n                  maturation environment is essential for the maturation of iPSC-derived cardiomyocytes to better model genetic cardiac diseases like DCM and provide valuable insights for future therapeutic strategies.\n                <\/jats:p>","DOI":"10.1101\/2025.08.11.669708","type":"posted-content","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T23:00:18Z","timestamp":1755298818000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>In vivo<\/i>\n                  bioreactor matures iPSC-CMs for MLP disease modeling"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-2194","authenticated-orcid":false,"given":"Sean A.","family":"Murphy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunsik","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattraranee","family":"Limphong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5475-5922","authenticated-orcid":false,"given":"Dong I.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-2778","authenticated-orcid":false,"given":"Chulan","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025081811200863000_2025.08.11.669708v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81878-4"},{"key":"2025081811200863000_2025.08.11.669708v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.040"},{"key":"2025081811200863000_2025.08.11.669708v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.089"},{"key":"2025081811200863000_2025.08.11.669708v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.10.014"},{"key":"2025081811200863000_2025.08.11.669708v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/srep19111"},{"key":"2025081811200863000_2025.08.11.669708v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"2025081811200863000_2025.08.11.669708v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.10.009"},{"key":"2025081811200863000_2025.08.11.669708v1.8","doi-asserted-by":"publisher","DOI":"10.1113\/JP276754"},{"key":"2025081811200863000_2025.08.11.669708v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009305"},{"key":"2025081811200863000_2025.08.11.669708v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112330"},{"key":"2025081811200863000_2025.08.11.669708v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01226-6"},{"key":"2025081811200863000_2025.08.11.669708v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/term.3188"},{"key":"2025081811200863000_2025.08.11.669708v1.13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62862"},{"key":"2025081811200863000_2025.08.11.669708v1.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908679"},{"key":"2025081811200863000_2025.08.11.669708v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21957-z"},{"key":"2025081811200863000_2025.08.11.669708v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.04.019"},{"key":"2025081811200863000_2025.08.11.669708v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2524"},{"key":"2025081811200863000_2025.08.11.669708v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0016-3"},{"key":"2025081811200863000_2025.08.11.669708v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01946-x"},{"key":"2025081811200863000_2025.08.11.669708v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"2025081811200863000_2025.08.11.669708v1.21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.15.1867"},{"key":"2025081811200863000_2025.08.11.669708v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046413"},{"key":"2025081811200863000_2025.08.11.669708v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.032"},{"key":"2025081811200863000_2025.08.11.669708v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.04.077"},{"key":"2025081811200863000_2025.08.11.669708v1.25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300558"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.11.669708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:21:04Z","timestamp":1768468864000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.11.669708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":25,"URL":"https:\/\/doi.org\/10.1101\/2025.08.11.669708","relation":{},"subject":[],"published":{"date-parts":[[2025,8,15]]},"subtype":"preprint"}}