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Erythropoietin improves pulmonary hypertension by promoting the homing and differentiation of bone marrow mesenchymal stem cells in lung tissue

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Abstract

Pulmonary arterial hypertension (PAH) is a chronic disease thatultimately progresses to right-sided heart failure and death. Erythropoietin (EPO) has been shown to have therapeutic potential in cardiovascular diseases, including PAH. In this study, we aimed to investigate the improvement effect of EPO pretreated bone marrow mesenchymal stem cells (BMSCs) on PAH. BMSCs were obtained from the bone marrow of male SD rats. Female rats were randomly divided into six groups, including control group, monocrotaline (MCT)-induced group, and four groups with different doses of EPO pretreated BMSCs. Lung tissue was taken for testing at 2 weeks of treatment. Our results showed EPO promoted homing and endothelial cell differentiation of BMSCs in the lung tissues of PAH rats. EPO and BMSCs treatment attenuated pulmonary arterial pressure, polycythemia, and pulmonary artery structural remodeling. Furthermore, BMSCs inhibited pulmonary vascular endothelial-to-mesenchymal transition (EndoMT) in PAH rats, which was further suppressed by EPO in a concentration-dependent manner. Meanwhile, EPO and BMSC treatment elevated pulmonary angiogenesis in PAH rats. BMSCs inhibited TNF-α, IL-1β, IL-6, and MCP-1 in lung tissues of PAH rats, which was further decreased by EPO in a concentration-dependent manner. Thus, EPO improved pulmonary hypertension (PH) by promoting the homing and differentiation of BMSCs in lung tissue.

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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by a Grant from the Key Project of Sichuan Science and Technology Agency (No. 2020YFQ0042) and the National Natural Science Foundation of China (No. 82174226).

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Authors and Affiliations

  1. Institute for Laboratory Animal Research, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China

    Zhendong Zhong

  2. Department of Gastroenterology, People’s Hospital of Tibet Autonomous Region, Lhasa, 850000, Tibet, China

    Kang Li

  3. School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 230041, Sichuan, China

    Chongyang Shen

  4. Department of Biology, New York University, 100 Washington Square E, New York, NY, 10003, United States of America

    Yuxiao Ma

  5. Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32# W. Sec 2,1St Ring Rd., Chengdu, 610072, Sichuan, China

    Lu Guo

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Animals and experimental protocol were conducted according to the guidelines and ethical standards of the Animal Care and Use Ethics Committees of West China Hospital of Sichuan University (20230806001). Animal studies followed the ARRIVE 2.0 guidelines.

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Zhong, Z., Li, K., Shen, C. et al. Erythropoietin improves pulmonary hypertension by promoting the homing and differentiation of bone marrow mesenchymal stem cells in lung tissue. Human Cell 37, 214–228 (2024). https://doi.org/10.1007/s13577-023-01009-y

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