EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Arne Jensen¹  Pierre Arsène²  Bernd Giebel³  Tobias Tertel³  Robin Dittrich³ 

[1] Brain Repair UG Campus Clinic, Gynaecology, Ruhr University Bochum, Bochum, Germany;Exosla Limited, Cambridge, United Kingdom;Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;

关键词: exosomes;    EV products;    iPSC-derived MSCs;    heterogeneity;    immune modulation;    quality control;   

DOI  :  10.3389/fcell.2023.1282860

 received in 2023-08-24, accepted in 2023-10-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in diverse clinical settings, largely due to their ability to produce extracellular vesicles (EVs). These EVs play a pivotal role in modulating immune responses, transforming pro-inflammatory cues into regulatory signals that foster a pro-regenerative milieu. Our previous studies identified the variability in the immunomodulatory effects of EVs sourced from primary human bone marrow MSCs as a consistent challenge. Given the limited proliferation of primary MSCs, protocols were advanced to derive MSCs from GMP-compliant induced pluripotent stem cells (iPSCs), producing iPSC-derived MSCs (iMSCs) that satisfied rigorous MSC criteria and exhibited enhanced expansion potential. Intriguingly, even though obtained iMSCs contained the potential to release immunomodulatory active EVs, the iMSC-EV products displayed batch-to-batch functional inconsistencies, mirroring those from bone marrow counterparts. We also discerned variances in EV-specific protein profiles among independent iMSC-EV preparations. Our results underscore that while iMSCs present an expansive growth advantage, they do not overcome the persistent challenge of functional variability of resulting MSC-EV products. Once more, our findings accentuate the crucial need for batch-to-batch functional testing, ensuring discrimination of effective and ineffective MSC-EV products for considered downstream applications.

【 授权许可】

Unknown   
Copyright © 2023 Tertel, Dittrich, Arsène, Jensen and Giebel.