A 3D culture system improves the yield of MSCs-derived extracellular vesicles and enhances their therapeutic efficacy for heart repair - 28/03/23

Doi : 10.1016/j.biopha.2023.114557

Ling Sun ^a,^b,^{^{1
The authors contributed equally to this study}}, Yuan Ji ^a,^b,^{^{1
The authors contributed equally to this study}}, Boyu Chi ^a,^c,^{^{1
The authors contributed equally to this study}}, Tingting Xiao ^a, Chenkai Li ^a, Xuejiao Yan ^a,^b, Xu Xiong ^d, Lipeng Mao ^a,^c, Dabei Cai ^a,^c, Ailin Zou ^a, Yu Wang ^a, Le Zhang ^e,^⁎ , Liming Tang ^f,^⁎ , Qingjie Wang ^a,^b,^⁎
^a Institute of Cardiovascular Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical Universityō, Changzhou, 213003 Jiangsu, China
^b Department of Cardiology, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213003 Jiangsu, China
^c Dalian Medical University, Dalian, 116000 Liaoning, China
^d Institute of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering, Changzhou, 213003 Jiangsu, China
^e Department of Neonatology, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214023 Jiangsu, China
^f Center of Gastrointestinal Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213003 Jiangsu, China

^⁎Corresponding authors.^⁎Corresponding author at: Institute of Cardiovascular Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China.Institute of Cardiovascular Disease, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityChangzhouJiangsu213003China.

Abstract

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.

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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Graphical Abstract

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Highlights

•	The yield of 3D-EVs was higher, with biofunctions similar to those of 2D-EVs.
•	3D-EVs repressed the apoptosis and facilitated angiogenesis.
•	3D-EVs regulated the transition of macrophage subpopulations after cardiac injury.
•	3D-EVs improved cardiac function in the AMI rats.
•	The culture system shows a great potential to be replicated in clinical practice.

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Keywords : Extracellular vesicles, Acute myocardial infarction, Mesenchymal stem cells, Three-dimensional culture system

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Vol 161

Article 114557- mai 2023 Retour au numéro

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A 3D culture system improves the yield of MSCs-derived extracellular vesicles and enhances their therapeutic efficacy for heart repair - 28/03/23

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