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, and Dino Di Carlo
bioRxiv, May 2023
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.
Topics
Cell Therapy, Extracellular Vesicles
Cell Types
Mouse MSCs
Instruments
SONY SH800, ImageStream10X Chromium