期刊论文详细信息
International Journal of Molecular Sciences
Culture Condition of Bone Marrow Stromal Cells Affects Quantity and Quality of the Extracellular Vesicles
Edwin M. Horwitz1  Takashi Kaito2  Masahiro Iwamoto3  Cierra A. Clark3  Satoru Otsuru3  Amanda L. Scheiber3  Yuka Imamura Kawasawa4 
[1] Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA 30322, USA;Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA;Departments of Pharmacology and Biochemistry and Molecular Biology, Institute of Personalized Medicine, Penn State University, College of Medicine, Hershey, PA 17033, USA;
关键词: bone marrow stromal cells (BMSCs);    extracellular vesicles (EVs);    miRNAs;    culture condition;   
DOI  :  10.3390/ijms23031017
来源: DOAJ
【 摘 要 】

Extracellular vesicles (EVs) released by bone marrow stromal cells (BMSCs) have been shown to act as a transporter of bioactive molecules such as RNAs and proteins in the therapeutic actions of BMSCs in various diseases. Although EV therapy holds great promise to be a safer cell-free therapy overcoming issues related to cell therapy, manufacturing processes that offer scalable and reproducible EV production have not been established. Robust and scalable BMSC manufacturing methods have been shown to enhance EV production; however, the effects on EV quality remain less studied. Here, using human BMSCs isolated from nine healthy donors, we examined the effects of high-performance culture media that can rapidly expand BMSCs on EV production and quality in comparison with the conventional culture medium. We found significantly increased EV production from BMSCs cultured in the high-performance media without altering their multipotency and immunophenotypes. RNA sequencing revealed that RNA contents in EVs from high-performance media were significantly reduced with altered profiles of microRNA enriched in those related to cellular growth and proliferation in the pathway analysis. Given that pre-clinical studies at the laboratory scale often use the conventional medium, these findings could account for the discrepancy in outcomes between pre-clinical and clinical studies. Therefore, this study highlights the importance of selecting proper culture conditions for scalable and reproducible EV manufacturing.

【 授权许可】

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