High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia
Due to their immunomodulatory function, mesenchymal stromal cells (MSCs) are a promising therapeutic with the potential to treat neuroinflammation associated with neurodegenerative diseases. This function is mediated by secreted extracellular vesicles (MSC-EVs). Despite established safety, MSC clini...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-07-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24000902 |
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| author | Andrew M. Larey Thomas M. Spoerer Kanupriya R. Daga Maria G. Morfin Hannah M. Hynds Jana Carpenter Kelly M. Hines Ross A. Marklein |
| author_facet | Andrew M. Larey Thomas M. Spoerer Kanupriya R. Daga Maria G. Morfin Hannah M. Hynds Jana Carpenter Kelly M. Hines Ross A. Marklein |
| author_sort | Andrew M. Larey |
| collection | DOAJ |
| description | Due to their immunomodulatory function, mesenchymal stromal cells (MSCs) are a promising therapeutic with the potential to treat neuroinflammation associated with neurodegenerative diseases. This function is mediated by secreted extracellular vesicles (MSC-EVs). Despite established safety, MSC clinical translation has been unsuccessful due to inconsistent clinical outcomes resulting from functional heterogeneity. Current approaches to mitigate functional heterogeneity include ‘priming’ MSCs with inflammatory signals to enhance function. However, comprehensive evaluation of priming and its effects on MSC-EV function has not been performed. Furthermore, clinical translation of MSC-EV therapies requires significant manufacturing scale-up, yet few studies have investigated the effects of priming in bioreactors. As MSC morphology has been shown to predict their immunomodulatory function, we screened MSC morphological response to an array of priming signals and evaluated MSC-EV identity and potency in response to priming in flasks and bioreactors. We identified unique priming conditions corresponding to distinct morphologies. These conditions demonstrated a range of MSC-EV preparation quality and lipidome, allowing us to discover a novel MSC-EV manufacturing condition, as well as gain insight into potential mechanisms of MSC-EV microglia modulation. Our novel screening approach and application of priming to MSC-EV bioreactor manufacturing informs refinement of larger-scale manufacturing and enhancement of MSC-EV function. |
| first_indexed | 2024-04-24T20:25:31Z |
| format | Article |
| id | doaj.art-117fb0ce6fda42fcb4c68978057c974e |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T20:25:31Z |
| publishDate | 2024-07-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-117fb0ce6fda42fcb4c68978057c974e2024-03-22T05:40:20ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-07-0137153171High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microgliaAndrew M. Larey0Thomas M. Spoerer1Kanupriya R. Daga2Maria G. Morfin3Hannah M. Hynds4Jana Carpenter5Kelly M. Hines6Ross A. Marklein7School of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, GA, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA, USASchool of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, GA, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA, USASchool of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, GA, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA, USARegenerative Bioscience Center, University of Georgia, Athens, GA, USADepartment of Chemistry, University of Georgia, Athens, GA, USADepartment of Chemistry, University of Georgia, Athens, GA, USADepartment of Chemistry, University of Georgia, Athens, GA, USASchool of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, GA, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA; Corresponding author. Current address: U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20903, USA.Due to their immunomodulatory function, mesenchymal stromal cells (MSCs) are a promising therapeutic with the potential to treat neuroinflammation associated with neurodegenerative diseases. This function is mediated by secreted extracellular vesicles (MSC-EVs). Despite established safety, MSC clinical translation has been unsuccessful due to inconsistent clinical outcomes resulting from functional heterogeneity. Current approaches to mitigate functional heterogeneity include ‘priming’ MSCs with inflammatory signals to enhance function. However, comprehensive evaluation of priming and its effects on MSC-EV function has not been performed. Furthermore, clinical translation of MSC-EV therapies requires significant manufacturing scale-up, yet few studies have investigated the effects of priming in bioreactors. As MSC morphology has been shown to predict their immunomodulatory function, we screened MSC morphological response to an array of priming signals and evaluated MSC-EV identity and potency in response to priming in flasks and bioreactors. We identified unique priming conditions corresponding to distinct morphologies. These conditions demonstrated a range of MSC-EV preparation quality and lipidome, allowing us to discover a novel MSC-EV manufacturing condition, as well as gain insight into potential mechanisms of MSC-EV microglia modulation. Our novel screening approach and application of priming to MSC-EV bioreactor manufacturing informs refinement of larger-scale manufacturing and enhancement of MSC-EV function.http://www.sciencedirect.com/science/article/pii/S2452199X24000902Mesenchymal stromal cellHigh throughput screeningExtracellular vesicleBioreactorMicrogliaLipidomics |
| spellingShingle | Andrew M. Larey Thomas M. Spoerer Kanupriya R. Daga Maria G. Morfin Hannah M. Hynds Jana Carpenter Kelly M. Hines Ross A. Marklein High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia Bioactive Materials Mesenchymal stromal cell High throughput screening Extracellular vesicle Bioreactor Microglia Lipidomics |
| title | High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia |
| title_full | High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia |
| title_fullStr | High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia |
| title_full_unstemmed | High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia |
| title_short | High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia |
| title_sort | high throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor based manufacturing of extracellular vesicles that modulate microglia |
| topic | Mesenchymal stromal cell High throughput screening Extracellular vesicle Bioreactor Microglia Lipidomics |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24000902 |
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