Continuous nutrient supply culture strategy controls multivesicular endosomes pathway and anti-photo-aging miRNA cargo loading of extracellular vesicles

Lihao Chen; Weihan Xie; Keke Wu; Yuan Meng; Yijun He; Jiawei Cai; Yuan Jiang; Qi Zhao; Yixi Yang; Minru Zhang; Manping Lu; Shaozhang Lin; Lin Liang; Zhiyong Zhang

doi:10.1177/20417314231197604

Journal of Tissue Engineering (Sep 2023)

Continuous nutrient supply culture strategy controls multivesicular endosomes pathway and anti-photo-aging miRNA cargo loading of extracellular vesicles

Lihao Chen,
Weihan Xie,
Keke Wu,
Yuan Meng,
Yijun He,
Jiawei Cai,
Yuan Jiang,
Qi Zhao,
Yixi Yang,
Minru Zhang,
Manping Lu,
Shaozhang Lin,
Lin Liang,
Zhiyong Zhang

Affiliations

Lihao Chen: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Weihan Xie: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Keke Wu: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Yuan Meng: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Yijun He: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Jiawei Cai: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Yuan Jiang: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Qi Zhao: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Yixi Yang: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Minru Zhang: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Manping Lu: Yue Dong Hospital District of Third Affiliated Hospital of Sun Yat-Sen University, Meizhou, Guangdong, China
Shaozhang Lin: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Lin Liang: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China
Zhiyong Zhang: Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, Department of Orthopaedic Surgery, Medical Technology and Related Equipment Research for Spinal Injury Treatment, City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China

DOI: https://doi.org/10.1177/20417314231197604
Journal volume & issue: Vol. 14

Abstract

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Extracellular vesicle (EV) therapy recently had shown significant efficacy in various diseases. Serum starvation culture (SC) is one of the most widely used methods for collecting EVs. However, SC may cause inadvertent effects and eventually dampen the therapeutic potential of EVs. Therefore, we developed a novel method for EV collection, continuous nutrient supply culture (CC), which can provide an optimal condition for mesenchymal stem cells (MSCs) by continuously supplying essential nutrients to MSCs. By comparing with SC strategy, we revealed that CC could maintain CC-MSCs in a normal autophagy and apoptotic state, which reduced the shunting of EV precursors in cells and useless information material carried by EVs. In CC-MSCs, the expression levels of endosomal sorting complexes required for transport (ESCRT) and targeting GTPase27 (Rab27) were upregulated compared to those in SC-MSCs. Besides, we analyzed the membrane transport efficiency of EV formation, which demonstrated the CC strategy could promote the formation of EV precursors and the release of EVs. In addition, miRNA analysis revealed that CC-EVs were enriched with anti-chronic inflammatory factors, which could inhibit the nuclear factor kappa-B (NF-κB) pathway, mitigate chronic inflammation, and effectively repair skin photo-aging damage.

Published in Journal of Tissue Engineering

ISSN: 2041-7314 (Online)
Publisher: SAGE Publishing
Country of publisher: United Kingdom
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://journals.sagepub.com/home/tej

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