Optimizing Cell Therapy by Sorting Cells with High Extracellular Vesicle Secretion

Doyeon Koo; Xiao Cheng; Shreya Udani; Dashuai Zhu; Junlang Li; Brian Hall; Natalie Tsubamoto; Shiqi Hu; Jina Ko; Ke Cheng; Dino Di Carlo

doi:10.1101/2023.05.29.542772

Optimizing Cell Therapy by Sorting Cells with High Extracellular Vesicle Secretion

bioRxiv [Preprint]. 2023 May 30:2023.05.29.542772. doi: 10.1101/2023.05.29.542772.

Authors

Doyeon Koo¹, Xiao Cheng^{2

3}, Shreya Udani¹, Dashuai Zhu^{2

3}, Junlang Li^{2

3}, Brian Hall⁴, Natalie Tsubamoto¹, Shiqi Hu^{2

3}, Jina Ko^{5

6}, Ke Cheng^{2

3}, Dino Di Carlo^{1

7

8

9}

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles; Los Angeles, CA 90095, USA.
² Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University; Chapel Hill, NC 27599, and Raleigh, NC 27607, USA.
³ Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University; Raleigh, NC 27607, USA.
⁴ Cytek Biosciences; Fremont, CA 94538, USA.
⁵ Department of Pathology and Laboratory Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
⁶ Department of Bioengineering, University of Pennsylvania; Philadelphia, PA 19104, USA.
⁷ Jonsson Comprehensive Cancer Center, University of California, Los Angeles; Los Angeles, CA 90095, USA.
⁸ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles; Los Angeles, CA 90095, USA.
⁹ California NanoSystems Institute; Los Angeles, CA 90095, USA.

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. We developed a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach was applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibited distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintained high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improved 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.

Keywords: Extracellular vesicles; Lab on a particle; Mesenchymal stromal cells; Single-cell analysis; regenerative medicine.

Publication types

Preprint

Abstract

Publication types

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