Transplantation of induced pluripotent stem cells-derived cardiomyocytes combined with modified Taohong Siwu decoction improved heart repair after myocardial infarction

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Abstract

Objective

This study aimed to study whether modified Taohong Siwu decoction (MTHSWD) combined with human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs) transplantation can promote cardiac function in myocardial infarction (MI) nude mouse model and explore its possible mechanism.

Methods

The MI mouse model was established by the ligation of left anterior descending coronary artery. After 4 weeks of gavage of MTHSWD combined with iPS-CMs transplantation, the changes in heart function of mice were examined by echocardiography. The histological changes were observed by Masson's trichrome staining. The survival and differentiation of transplanted cells were detected by double immunofluorescence staining of human nuclear antigen (HNA) and cardiac troponin T (cTnT). The number of c-kit-positive cells in the infarct area were evaluated by immunofluorescent staining. The levels of stromal cell-derived factor 1 (SDF-1), stem cell factor (SCF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in infarcted myocardium tissues were detected by ELISA.

Results

MTHSWD combined with iPS-CMs transplantation can improve the heart function of MI mice, reduce the infarct size and collagen deposition in infarct area. By immunofluorescence double-label detection of HNA and cTnT, it was found that MTHSWD combined with iPS-CMs transplantation can improve the survival and maturation of iPS-CMs. In addition, MTHSWD combined with iPS-CMs transplantation can activate more endogenous c-kit positive cardiac mesenchymal cells, and significantly increase the content of SDF-1, SCF and VEGF in myocardial tissues.

Conclusions

The combination of MTHSWD with iPS-CMs transplantation promoted cardiac function of nude mice with MI by improving the survival and maturation of iPS-CMs in the infarct area, activating the endogenous c-kit positive cardiac mesenchymal cells, and increasing paracrine.

Related collections

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We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.

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Author and article information

Contributors

Yuan Yuan

Wei Huang

Hai-dong Guo

Journal

Journal ID (nlm-ta): Heliyon

Journal ID (iso-abbrev): Heliyon

Title: Heliyon

Publisher: Elsevier

ISSN (Electronic): 2405-8440

Publication date PMC-release: 20 February 2024

Publication date Collection: 29 February 2024

Publication date (Electronic): 20 February 2024

Volume: 10

Issue: 4

Electronic Location Identifier: e26700

Affiliations

[a ]Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

[b ]Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

[c ]Department of Chinese Internal Medicine, Dahua Hospital, Xuhui District, Shanghai, China

Author notes

[∗ ]Corresponding author. yuanyuan@ 123456shutcm.edu.cn

[∗∗ ]Corresponding author. huangwei363965069@ 123456qq.com

[∗∗∗ ]Corresponding author. Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. hdguo@ 123456shutcm.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2405-8440(24)02731-2 Publisher ID: e26700

DOI: 10.1016/j.heliyon.2024.e26700

PMC ID: 10906439

PubMed ID: 38434034

SO-VID: 5a514ff6-1f32-4ec9-a149-ecb5d5c3d7e7

License:

This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

History

Date received : 29 October 2022

Date revision received : 2 February 2024

Date accepted : 19 February 2024