EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro
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 f...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1282860/full |
| _version_ | 1797645799053590528 |
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| author | Tobias Tertel Robin Dittrich Pierre Arsène Arne Jensen Bernd Giebel |
| author_facet | Tobias Tertel Robin Dittrich Pierre Arsène Arne Jensen Bernd Giebel |
| author_sort | Tobias Tertel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T14:52:05Z |
| format | Article |
| id | doaj.art-a659b8ec4d35490fb4991592193e973e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-11T14:52:05Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a659b8ec4d35490fb4991592193e973e2023-10-30T09:17:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-10-011110.3389/fcell.2023.12828601282860EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitroTobias Tertel0Robin Dittrich1Pierre Arsène2Arne Jensen3Bernd Giebel4Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyExosla Limited, Cambridge, United KingdomBrain Repair UG Campus Clinic, Gynaecology, Ruhr University Bochum, Bochum, GermanyInstitute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyMesenchymal 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1282860/fullexosomesEV productsiPSC-derived MSCsheterogeneityimmune modulationquality control |
| spellingShingle | Tobias Tertel Robin Dittrich Pierre Arsène Arne Jensen Bernd Giebel 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 exosomes EV products iPSC-derived MSCs heterogeneity immune modulation quality control |
| title | EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro |
| title_full | EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro |
| title_fullStr | EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro |
| title_full_unstemmed | EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro |
| title_short | EV products obtained from iPSC-derived MSCs show batch-to-batch variations in their ability to modulate allogeneic immune responses in vitro |
| title_sort | ev products obtained from ipsc derived mscs show batch to batch variations in their ability to modulate allogeneic immune responses in vitro |
| topic | exosomes EV products iPSC-derived MSCs heterogeneity immune modulation quality control |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1282860/full |
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