Human umbilical cord mesenchymal stem cell transplantation for myocardial hypertrophy in mice

doi:10.12307/2022.762

Abstract

Abstract: BACKGROUND: As a common target organ damage in hypertension, left ventricular hypertrophy is an independent risk factor for high morbidity and mortality of cardiovascular and cerebrovascular diseases. Mesenchymal stem cells can promote tissue repair, regulate immune response, and can be used as seed cells for the treatment of cardiac hypertrophy.
OBJECTIVE: To observe the efficacy of intravenous injection of human umbilical cord mesenchymal stem cells in the treatment of myocardial hypertrophy in mice.
METHODS: (1) C57BL/6J mice were randomly divided into a sham operation group, a human umbilical cord mesenchymal stem cell group, and a PBS group. Among them, transverse aortic constriction was used to construct a C57BL/6J mouse cardiac hypertrophy model in the human umbilical cord mesenchymal stem cell group and the PBS group. The mice in the human umbilical cord mesenchymal stem cell group were injected with the cell suspension into the tail vein once a week for 4 weeks starting from the 5th week after the operation. The mice in the PBS group were injected with the same amount of PBS in the tail vein. At 6-11 weeks after operation, echocardiography was used to observe the cardiac function of the mice in each group. Hematoxylin-eosin staining and western blot assay were used to detect the degree of cardiomyocyte hypertrophy at 9, 10, and 11 weeks after surgery. (2) In vitro experiment, H9c2 cells hypertrophy was induced by isoproterenol. Afterwards, the human umbilical cord mesenchymal stem cells and hypertrophic H9c2 cells were co-cultured in TranswellTM chamber for 48 hours. F-actin staining was used to analyze H9c2 cells area. qRT-PCR was utilized to determine mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain in H9c2 cells.
RESULTS AND CONCLUSION: (1) The results of echocardiography confirmed that the left ventricular ejection fraction and left ventricular fraction shortening of mouse heart in the human umbilical cord mesenchymal stem cell group were significantly higher than those in the PBS group (P < 0.05). (2) Hematoxylin-eosin staining results showed that compared with the PBS group, the myocardial fibers in the human umbilical cord mesenchymal stem cell group were neatly arranged and the cross-sectional area of myocardial cells was significantly decreased (P < 0.05). (3) Western blot assay results showed that the protein expression levels of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain of mouse cardiomyocytes in the human umbilical cord mesenchymal stem cell group were significantly lower than those in the PBS group at the same time point (P < 0.01). (4) Compared with the isoproterenol group, the area of H9c2 cells after co-culture was significantly reduced (P < 0.01); the mRNA expression levels of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain in H9c2 cells were significantly decreased (P < 0.05). (5) Human umbilical cord mesenchymal stem cells can alleviate the occurrence of cardiac hypertrophy induced by pressure overload and improve the cardiac function of mice by inhibiting the expression of hypertrophy-related genes in cells.

Key words: human umbilical cord mesenchymal stem cells, mouse, transverse aortic constriction, cellular hypertrophy, cell co-culture, atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain

CLC Number:

Xie Liying, Liu Siqi, Wu Mingrui, Gao Erhe, Han Zhibo, Zuo Lin. Human umbilical cord mesenchymal stem cell transplantation for myocardial hypertrophy in mice[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(30): 4826-4833.

Figures/Tables 6

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