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This study aimed to investigate the cardioprotective role of MG53 on human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) in the context of myocardial ischemia\/reperfusion (I\/R).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In vitro<jats:italic>:<\/jats:italic> HiPSC-CMs were transfected with adenoviral MG53 (HiPSC-CMs<jats:sup>MG53<\/jats:sup>), in which the expression of MG53 can be controlled by doxycycline (Dox), and the cells were then exposed to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> to mimic ischemia\/reperfusion injury. In vivo<jats:italic>:<\/jats:italic> HiPSC-CMs<jats:sup>MG53<\/jats:sup> were transplanted into the peri-infarct region in NSG\u2122 mice after I\/R. After surgery, mice were treated with Dox (+\u2009Dox) to activate MG53 expression (sucrose as a control of -Dox) and then assessed by echocardiography and immunohistochemistry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>MG53 can be expressed in HiPSC-CM<jats:sup>MG53<\/jats:sup> and released into the culture medium after adding Dox. The cell survival rate of HiPSC-CM<jats:sup>MG53<\/jats:sup> was improved by Dox under the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> condition. After 14 and 28\u00a0days of ischemia\/reperfusion (I\/R), transplanted HiPSC-CMs<jats:sup>MG53<\/jats:sup>\u2009+\u2009Dox significantly improved heart function, including ejection fraction (EF) and fractional shortening (FS) in mice, compared to HiPSC-CMs<jats:sup>MG53<\/jats:sup>-Dox, and reduced the size of the infarction. Additionally, HiPSC-CM<jats:sup>MG53<\/jats:sup>\u2009+\u2009Dox mice demonstrated significant engraftment in the myocardium as shown by staining human nuclei-positive cells. In addition, the cell survival-related AKT signaling was found to be more active in HiPSC-CM<jats:sup>MG53<\/jats:sup>\u2009+\u2009Dox transplanted mice\u2019s myocardium compared to the HiPSC-CM<jats:sup>MG53<\/jats:sup>-Dox group. Notably, the Dox treatment did not cause harm to other organs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p> Inducible MG53 expression is a promising approach to enhance cell survival and engraftment of HiPSC-CMs for cardiac repair.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s12015-023-10596-0","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T07:03:11Z","timestamp":1689922991000},"page":"2420-2428","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Activation of MG53 Enhances Cell Survival and Engraftment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Injured Hearts"],"prefix":"10.1007","volume":"19","author":[{"given":"Ki Ho","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialiang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0872-1860","authenticated-orcid":false,"given":"Yigang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"issue":"25","key":"10596_CR1","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","volume":"76","author":"GA Roth","year":"2020","unstructured":"Roth, G. 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