Mesenchymal stem cells derived from CHIR99021 and TGF‑β induction remained on the colicomentum and improved cardiac function of a rat model of acute myocardium infarction

Zhang,Yusen; Zhang,Yanmin; Hu,Azhen; Meng,Fanhua; Cui,Peng; Li,Tianshi; Cui,Guanghui

doi:10.3892/etm.2024.12470

Mesenchymal stem cells derived from CHIR99021 and TGF‑β induction remained on the colicomentum and improved cardiac function of a rat model of acute myocardium infarction

Authors:
- Yusen Zhang
- Yanmin Zhang
- Azhen Hu
- Fanhua Meng
- Peng Cui
- Tianshi Li
- Guanghui Cui
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Affiliations: Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Shenzhen Key Laboratory of Drug Addiction and Safe Medication, Shenzhen PKU‑HKUST Medical Centre, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Reproductive Medical Centre, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Plastic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: March 4, 2024 https://doi.org/10.3892/etm.2024.12470
Article Number: 182
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK‑3 inhibitor CHIR99021 and TGF‑β was used to obtain mesenchymal stem cell (MSC)‑like cells from hiPSCs. During the induction process, the transcription of epithelial‑mesenchymal transition (EMT)‑related genes N‑cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E‑cadherin and pluripotency‑related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD‑dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC‑derived MSC‑like cells (hiPSC‑MSCs) expressed MSC‑related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC‑MSCs secreted angiogenic and immune‑regulatory factors and remained on the colicomentum for 3 weeks. Within an 11‑week period, four intraperitoneal hiPSC‑MSC injections (1x10⁷ cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC‑MSC‑induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC‑MSC treated rats. In conclusion, the CHIR99021 and TGF‑β combined induction was a rapid and effective method to obtain MSC‑like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC‑derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.

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