The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases

Zhang, Huan; Wan, Xueqi; Tian, Jinfan; An, Ziyu; Liu, Libo; Zhao, Xin; Zhou, Yuquan; Zhang, Lijun; Ge, Changjiang; Song, Xiantao

doi:10.1016/j.biopha.2023.115551

Biomedicine & Pharmacotherapy

2023

DOI: 10.1016/j.biopha.2023.115551

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The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases

Huan Zhang,

Xueqi Wan,

Jinfan Tian

et al.

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2024

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Cited by 2 publications

References 121 publications

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NQO1 promotes osteogenesis and suppresses angiogenesis in DPSCs via MAPK pathway modulation

Wang,

Yang,

Fan

et al. 2024

Stem Cell Res Ther

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NQO1 promotes osteogenesis and suppresses angiogenesis in DPSCs via MAPK pathway modulation

Wang,

Yang,

Fan

et al. 2024

Stem Cell Res Ther

View full text Add to dashboard Cite

Mass Production of Rg1-Loaded Small Extracellular Vesicles Using a 3D Bioreactor System for Enhanced Cardioprotective Efficacy of Doxorubicin-Induced Cardiotoxicity

Di,

Zhao,

Fan

et al. 2024

Pharmaceutics

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Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims to achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, sEVs were developed to deliver Ginsenoside Rg1 (Rg1), a compound derived from traditional Chinese medicine, Ginseng, that has cardioprotective properties but limited bioavailability, to enhance the treatment of DIC. Methods: The 3D bioreactor system with spinner flasks was used to expand human umbilical cord MSCs and collect MSC-conditioned medium. Subsequently, sEVs were isolated from the conditioned medium using differential ultra-centrifugation (dUC). The sEVs were loaded with Ginsenoside Rg1 by electroporation and evaluated for cardioprotective efficacy using Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining and live cell count of H9c2 cells under DIC. Results: Using the 3D bioreactor system with spinner flasks, the expansion of MSCs reached ~600 million, and the production of sEVs was up to 2.2 × 1012 particles in five days with significantly reduced bench work compared to traditional 2D flasks. With the optimized protocol, the Ginsenoside Rg1 loading efficiency of sEVs by electroporation was ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded sEVs had attenuated DOX-induced cardiotoxicity with reduced apoptosis compared to free Ginsenoside Rg1 or sEVs. Conclusions: The 3D culture system scaled up the production of sEVs, which facilitated the Rg1 delivery and attenuated cardiomyocyte apoptosis, suggesting a potential treatment of DOX-induced cardiotoxicity.

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The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases

Cited by 2 publications

References 121 publications

NQO1 promotes osteogenesis and suppresses angiogenesis in DPSCs via MAPK pathway modulation

NQO1 promotes osteogenesis and suppresses angiogenesis in DPSCs via MAPK pathway modulation

Mass Production of Rg1-Loaded Small Extracellular Vesicles Using a 3D Bioreactor System for Enhanced Cardioprotective Efficacy of Doxorubicin-Induced Cardiotoxicity

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