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Table 3 Bioreactor systems for MSC-EV production

From: Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions

In vitro system Origin of EVs Yield Harvest time Medium supplement Study
10-layer Nunc™ EasyFill™ Cell Factory™ (2D) systems (Thermo Fisher Scientific, USA) UC-MSC 1.36 × 109 ± 3.49 × 108 up to 5.96 × 109 ± 7.11 × 108 particles/mL 48 h over 6 days OxiumTMEXO [70]
Quantum (3D) bioreactor culture system (Terumo BCT, USA) BM MSC-derived Evs 1.04 × 1010 particles/mL 48 h over 12 days α MEM supplemented with 1% L-glutamine, 5% human platelet lysate, and 1% penicillin-strep- tomycin [31]
Microcarrier-based (2.5D) culture in stirred tank bioreactor UC-MSC 27-fold 48 h serum-/xenofree StemPro medium (A1067501; Life Technologies, USA) [52]
Microcarrier-based (2.5D) cultivation in spinner flask hBM-MSC 1 × 1011 particles/mL 48 h over 7 days 5% fetal bovine serum (FBS) [74]
Hollow fiber (3D) bioreactor (Fibercell Systems, USA) hBM-MSCs 5.5 × 1010 particles/mL 24 h over 25 days RoosterCollect-EV ser-/xeno-free medium (RoosterBio Inc., cat.#M2001) [71]
Microcarrier-based (2.5D) cultivation in Vertical-Wheel™ AD-MSC 3.1 ± 1.3 × 1011 48 h DMEM low glucose, 5% v/v UltraGRO™-PURE, Antibiotic–Antimycotic 1x [87]
BM-MSC 2.8 ± 0.1 × 1011
UC-MSC 4.1 ± 1.7 × 1011 EV particles