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Optimizing cell therapy by sorting cells with high extracellular vesicle secretion

Author

Listed:
  • Doyeon Koo

    (University of California, Los Angeles)

  • Xiao Cheng

    (University of North Carolina at Chapel Hill and North Carolina State University
    University of North Carolina at Chapel Hill and North Carolina State University)

  • Shreya Udani

    (University of California, Los Angeles)

  • Sevana Baghdasarian

    (University of California, Los Angeles)

  • Dashuai Zhu

    (Columbia University)

  • Junlang Li

    (Xsome Biotech)

  • Brian Hall

    (Cytek Biosciences)

  • Natalie Tsubamoto

    (University of California, Los Angeles)

  • Shiqi Hu

    (Columbia University)

  • Jina Ko

    (University of Pennsylvania
    University of Pennsylvania)

  • Ke Cheng

    (Columbia University)

  • Dino Di Carlo

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    California NanoSystems Institute)

Abstract

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.

Suggested Citation

  • Doyeon Koo & Xiao Cheng & Shreya Udani & Sevana Baghdasarian & Dashuai Zhu & Junlang Li & Brian Hall & Natalie Tsubamoto & Shiqi Hu & Jina Ko & Ke Cheng & Dino Di Carlo, 2024. "Optimizing cell therapy by sorting cells with high extracellular vesicle secretion," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49123-1
    DOI: 10.1038/s41467-024-49123-1
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    References listed on IDEAS

    as
    1. Bin Yu & Hekai Li & Zhaowenbin Zhang & Peier Chen & Ling Wang & Xianglin Fan & Xiaodong Ning & Yuxuan Pan & Feiran Zhou & Xinyi Hu & Jiang Chang & Caiwen Ou, 2023. "Extracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Dashuai Zhu & Zhenhua Li & Ke Huang & Thomas G. Caranasos & Joseph S. Rossi & Ke Cheng, 2021. "Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Rene Yu-Hong Cheng & Joseph de Rutte & Cade Ellis K. Ito & Andee R. Ott & Lucie Bosler & Wei-Ying Kuo & Jesse Liang & Brian E. Hall & David J. Rawlings & Dino Di Carlo & Richard G. James, 2023. "SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
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