| Autor: |
Kyung Min Lim, Sehee Kim, Jeonghun Yeom, Yujin Choi, Yoonjoo Lee, Jongyub An, Minchan Gil, Ahmed Abdal Dayem, Kyeongseok Kim, Geun-Ho Kang, Aram Kim, Kwonho Hong, Kyunggon Kim, Ssang-Goo Cho |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Advanced Research, Vol 47, Iss , Pp 57-74 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2090-1232 |
| DOI: |
10.1016/j.jare.2022.09.005 |
| Popis: |
Introduction: Mesenchymal stromal cells (MSCs) release extracellular vesicles (MSC-EVs) containing various cargoes. Although MSC-EVs show significant therapeutic effects, the low production of EVs in MSCs hinders MSC-EV-mediated therapeutic development. Objectives: Here, we developed an advanced three-dimensional (a3D) dynamic culture technique with exogenous transforming growth factor beta-3 (TGF-β3) treatment (T-a3D) to produce potent MSC-EVs. Methods: Our system enabled preparation of a highly concentrated EV-containing medium for efficient EV isolation and purification with higher yield and efficacy. Results: MSC spheroids in T-a3D system (T-a3D spheroids) showed high expression of CD9 and TGF-β3, which was dependent on TGF-β signaling. Treatment with EVs produced under T-a3D conditions (T-a3D-EVs) led to significantly improved migration of dermal fibroblasts and wound closure in an excisional wound model. The relative total efficacy (relative yield of single-batch EVs (10–11-fold) × relative regeneration effect of EVs (2–3-fold)) of T-a3D-EVs was approximately up to 33-fold higher than that of 2D-EVs. Importantly the quantitative proteomic analyses of the T-a3D spheroids and T-a3D-EVs supported the improved EV production as well as the therapeutic potency of T-a3D-EVs. Conclusion: TGF-β signalling differentially regulated by fluid shear stress produced in our system and exogenous TGF-β3 addition was confirmed to play an important role in the enhanced production of EVs with modified protein cargoes. We suggest that the T-a3D system leads to the efficient production of MSC-EVs with high potential in therapies and clinical development. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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