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In the current study, MSC\u2010like cells were derived from human\u2010induced pluripotent stem cells through valproic acid (VPA) induction and continuous cell passages. The derived spindle\u2010like cells expressed MSC\u2010related markers, secreted angiogenic and immune\u2010regulatory factors, and could be induced to experience chondrogenic and adipogenic differentiation. During the induction process, expression of epithelial\u2010to\u2010mesenchymal transition\u2010 (EMT\u2010) related gene N\u2010cadherin and vimentin was upregulated to a very high level, and the expression of pluripotency\u2010related genes Sox2 and Oct4 was downregulated or remained unchanged, indicating that VPA initiated EMT by upregulating the expression of EMT promoting genes and downregulating that of pluripotency\u2010related genes. Two and four intravenous hiPSC\u2010MSC injections (10<jats:sup>6<\/jats:sup> cells\/per injections) were provided, respectively, to model rats one week after acute myocardial infarction (AMI). Cardiac function parameters were dynamically monitored during a 12\u2010week period. Two and four cell injections significantly the improved left ventricular ejection fraction and left ventricular fractional shortening; four\u2010injection markedly stimulated angiogenesis reduced the scar size and cell apoptosis number in the scar area in comparison with that of the untreated control model rats. Although the difference was insignificant, the hiPSC\u2010MSC administration delayed the increase of left ventricular end\u2010diastolic dimension to different extents compared with that of the PBS\u2010injection control. No perceptible immune reaction symptom or hiPSC\u2010MSC\u2010induced tumour formation was found over 12 weeks. Compared with the PBS\u2010injection control, four injections produced better outcome than two injections; as a result, at least four rounds of MSC injections were suggested for AMI treatment.<\/jats:p>","DOI":"10.1155\/2020\/2863501","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T03:50:19Z","timestamp":1608263419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multiple Intravenous Injections of Valproic Acid\u2010Induced Mesenchymal Stem Cell from Human\u2010Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model"],"prefix":"10.1155","volume":"2020","author":[{"given":"Shuyuan","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanhua","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4975-5637","authenticated-orcid":false,"given":"Yun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-7198","authenticated-orcid":false,"given":"Guanghui","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0102.101442"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908610"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.10.004"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.952507"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022949"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.243147"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.03.034"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060186"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.575118"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.06.055"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.086074"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000137878.26174.66"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000118601.37875.AC"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/181020"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i5.552"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2011.06.003"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.12.004"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2014.0344"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.004"},{"key":"e_1_2_9_20_2","first-page":"4214","article-title":"Combined therapy with atorvastatin and atorvastatin-pretreated mesenchymal stem cells enhances cardiac performance after acute myocardial infarction by activating SDF-1\/CXCR4 axis","volume":"11","author":"Tian X. 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