{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:33:31Z","timestamp":1787873611572,"version":"build-2784847793"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01HL142627"],"award-info":[{"award-number":["R01HL142627"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20TPA35490001"],"award-info":[{"award-number":["20TPA35490001"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL148165"],"award-info":[{"award-number":["R01HL148165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Cellular transplantation has emerged as promising approach for treating cardiac diseases. However, a poor engraftment rate limits our understanding on how transplanted cardiomyocytes contribute to cardiac function in the recipient\u2019s heart. Methods: The CRISPR\/Cas9 technique was employed for stable and constitutive gene expression in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Myocardial infarction was induced in adult immunodeficient mice, followed by intramyocardial injection of hiPSC-CMs expressing either CCND2\/channelrhodopsin 2 (hiPSC-CCND2OE\/ChR2OECMs) or CCND2\/luciferase (hiPSC-CCND2OE\/LuciOECMs). Six months later, hemodynamics and intramural electrocardiogram were recorded upon blue light illuminations in anesthetized, open-chest mice. Results: Blue light resets automaticity of spontaneously beating hiPSC-CCND2OE\/ChR2OECMs in culture, but not that of hiPSC-CCND2OE\/LuciOECMs. Response to blue light was also observed in mice carrying large (&gt;106 cells) intracardiac grafts of hiPSC-CCND2OE\/ChR2OECM but not in mice carrying hiPSC-CCND2OE\/LuciOECMs. The former exhibited single premature ventricular contractions upon light illumination or ventricular quadrigeminy upon second-long illuminations. At the onset of premature ventricular contractions, maximal systolic ventricular pressure decreased while ventricular volume rose concomitantly. Light-induced changes reversed upon resumption of sinus rhythm. Conclusions: We established an in vivo model for optogenetic-based modulation of the excitability of donor cardiomyocytes in a functional, reversible, and localized manner. This approach holds unique value for studying electromechanical coupling and molecular interactions between donor cardiomyocytes and recipient hearts in live animals.<\/jats:p>","DOI":"10.3390\/cells11060951","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Optogenetic Control of Engrafted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Live Mice: A Proof-of-Concept Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Jyotsna","family":"Joshi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"},{"name":"Department of Cardiology, Northern Jiangsu People\u2019s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-6943","authenticated-orcid":false,"given":"Michael","family":"Rubart","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0955-6868","authenticated-orcid":false,"given":"Xiaoping","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari P.","family":"Chaliki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis R.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5217-7789","authenticated-orcid":false,"given":"Wuqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"},{"name":"Center for Regenerative Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/jamacardio.2016.2225","article-title":"Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review","volume":"1","author":"Nguyen","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1001\/jamacardio.2016.2750","article-title":"Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review","volume":"1","author":"Nguyen","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1152\/physrev.00019.2015","article-title":"Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue","volume":"96","author":"Golpanian","year":"2016","journal-title":"Physiol. 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