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Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling

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Abstract

Background

Bone marrow mesenchymal stem cells (BMSCs) transplantation therapy providing a great hope for the recovery of myocardial ischemic hypoxic injury. However, the microenvironment after myocardial injury is not conducive to the survival of BMSCs, which limits the therapeutic application of BMSCs. Our previous study has confirmed that the survival of BMSCs cells in the glucose and serum deprivation under hypoxia (GSDH) is increased after Andrographolide (AG) pretreatment, but whether this treatment could improve the effect of BMSCs in repairing of myocardial injury has not been verified.

Methods and result

We first treated H9C2 with GSDH to simulate the microenvironment of myocardial injury in vitro, then we pretreated rat primary BMSCs with AG, and collected conditioned medium derived from BMSCs (BMSCs-CM) and conditioned medium derived from AG-pretreated BMSCs (AG-BMSCs-CM) after GSDH treatment. And they were used to treat H9C2 cells under GSDH to further detect oxidative stress and metabolic changes. The results showed that AG-BMSCs-CM could be more advantageous for cardiomyocyte injury repair than BMSCs-CM, as indicated by the decrease of apoptosis rate and oxidative stress. The changes of mitochondria and lipid droplets results suggested that AG-BMSCs-CM can regulate metabolic remodeling of H9C2 cells to repair cell injury, and that AMPK was activated during this process.

Conclusions

This study demonstrates, for the first time, the protective effect of AG-BMSCs-CM on GSDH-induced myocardial cell injury, providing a potential therapeutic strategy for clinical application.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81970244).

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YS prepared the article and acquired the data. HX, BT and QY were involved in article preparation. HH, JZ and JT conceived and designed the project. HL analyzed and interpreted the data. YS and HH wrote the paper.

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Correspondence to Jing Zhu.

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11033_2023_8250_MOESM1_ESM.jpg

Supplementary material 1 (JPG 545.7 kb)—Fig. S1Schematic of the potential mechanism by whichAG-BMSCs-CM improves the anti-apoptosis and anti-oxidative stress effects ofcardiomyocyte under GSDH.

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Sun, Y., Xu, H., Tan, B. et al. Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling. Mol Biol Rep 50, 2651–2662 (2023). https://doi.org/10.1007/s11033-023-08250-6

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