Open AccessEngineering extracellular vesicles by three‐dimensional dynamic culture of human mesenchymal stem cells
Author(s) -
Yuan Xuegang,
Sun Li,
Jeske Richard,
Nkosi Dingani,
York Sara B.,
Liu Yuan,
Grant Samuel C.,
Meckes David G.,
Li Yan
Publication year - 2022
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12235
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , microvesicles , extracellular vesicles , extracellular vesicle , downregulation and upregulation , exosome , stem cell , endosome , biogenesis , transcriptome , chemistry , biology , intracellular , microrna , gene expression , biochemistry , gene
Human mesenchymal stem cell (hMSC) derived extracellular vesicles (EVs) have shown therapeutic potential in recent studies. However, the corresponding therapeutic components are largely unknown, and scale‐up production of hMSC EVs is a major challenge for translational applications. In the current study, hMSCs were grown as 3D aggregates under wave motion to promote EV secretion. Results demonstrate that 3D hMSC aggregates promote activation of the endosomal sorting complexes required for transport (ESCRT)‐dependent and ‐independent pathways. mRNA sequencing revealed global transcriptome alterations for 3D hMSC aggregates. Compared to 2D‐hMSC‐EVs, the quantity of 3D‐hMSC‐EVs was enhanced significantly (by 2‐fold), with smaller sizes, higher miR‐21 and miR‐22 expression, and an altered protein cargo (e.g., upregulation of cytokines and anti‐inflammatory factors) uncovered by proteomics analysis, possibly due to altered EV biogenesis. Functionally, 3D‐hMSC‐EVs rejuvenated senescent stem cells and exhibited enhanced immunomodulatory potentials. In summary, this study provides a promising strategy for scalable production of high‐quality EVs from hMSCs with enhanced therapeutic potential.