{"doi":"10.1007/s12015-023-10596-0","title":"Activation of MG53 Enhances Cell Survival and Engraftment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Injured Hearts","abstract":"Abstract Background and Objective Our previous studies demonstrated that MG53 protein can protect the myocardium, but its use as a therapeutic is challenging due to its short half-life in blood circulation. 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). Methods In vitro : HiPSC-CMs were transfected with adenoviral MG53 (HiPSC-CMs MG53 ), in which the expression of MG53 can be controlled by doxycycline (Dox), and the cells were then exposed to H 2 O 2 to mimic ischemia/reperfusion injury. In vivo : HiPSC-CMs MG53 were transplanted into the peri-infarct region in NSG™ mice after I/R. After surgery, mice were treated with Dox (+ Dox) to activate MG53 expression (sucrose as a control of -Dox) and then assessed by echocardiography and immunohistochemistry. Results MG53 can be expressed in HiPSC-CM MG53 and released into the culture medium after adding Dox. The cell survival rate of HiPSC-CM MG53 was improved by Dox under the H 2 O 2 condition. After 14 and 28 days of ischemia/reperfusion (I/R), transplanted HiPSC-CMs MG53 + Dox significantly improved heart function, including ejection fraction (EF) and fractional shortening (FS) in mice, compared to HiPSC-CMs MG53 -Dox, and reduced the size of the infarction. Additionally, HiPSC-CM MG53 + Dox 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 MG53 + Dox transplanted mice’s myocardium compared to the HiPSC-CM MG53 -Dox group. Notably, the Dox treatment did not cause harm to other organs. Conclusion Inducible MG53 expression is a promising approach to enhance cell survival and engraftment of HiPSC-CMs for cardiac repair. Graphical Abstract","journal":"Stem Cell Reviews and Reports","year":2023,"id":375176,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":936212,"name":"Xingyu He","orcid":"0000-0002-6620-6074","position":1,"is_corresponding":false},{"id":455446,"name":"Lin Jiang","orcid":"0000-0002-0947-1760","position":2,"is_corresponding":false},{"id":554568,"name":"Hua Zhu","orcid":"0000-0001-7136-7326","position":3,"is_corresponding":false},{"id":281172,"name":"Jialiang Liang","orcid":"0000-0001-8033-741X","position":4,"is_corresponding":false},{"id":297847,"name":"Yigang Wang","orcid":"0000-0002-0872-1860","position":5,"is_corresponding":false},{"id":341623,"name":"Jianjie Ma","orcid":"0000-0003-3865-6112","position":6,"is_corresponding":false},{"id":665161,"name":"Ki Ho Park","orcid":"0000-0002-6193-9826","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:16:19.336238Z","pmid":"37477774","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}