A 3D culture system improves the yield of MSCs-derived extracellular vesicles and enhances their therapeutic efficacy for heart repair

3D 培养系统可提高 MSCs 衍生的细胞外囊泡的产量并增强其对心脏修复的治疗效果

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作者:Ling Sun, Yuan Ji, Boyu Chi, Tingting Xiao, Chenkai Li, Xuejiao Yan, Xu Xiong, Lipeng Mao, Dabei Cai, Ailin Zou, Yu Wang, Le Zhang, Liming Tang, Qingjie Wang

Background

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), due to their inner functional substances, have shown great value in treating acute myocardial infarction (AMI). However, their clinical application is limited by a low yield. In the present study, we cultured EVs using a hollow fiber bioreactor-based three-dimensional (3D) system, and assessed their therapeutic effectiveness on AMI.

Conclusions

The hollow fiber 3D culture system can increase the yield of MSCs-derived EVs to render a strong cardioprotective effect in AMI rats.

Methods

The MSCs separated from fresh human umbilical cord were planted into the flasks of two systems: two-dimensional (2D) culture and hollow-fiber-bioreactor based 3D culture. EVs were extracted from the culture supernatants. Characteristics and yields of EVs from two culture systems, namely 2D-EVs and 3D-EVs, were compared. A rat model of AMI was built up to assess their therapeutic efficacy on AMI.

Results

The yield of 3D-EVs was higher, with biofunctions similar to those of 2D-EVs. 3D-EVs repressed the apoptosis of cardiomyocytes, facilitated angiogenesis, and regulated the transition of macrophage subpopulations after myocardial infarction, and eventually improved cardiac function in the AMI rats. Conclusions: The hollow fiber 3D culture system can increase the yield of MSCs-derived EVs to render a strong cardioprotective effect in AMI rats.

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