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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 Nuncâ„¢ EasyFillâ„¢ Cell Factoryâ„¢ (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-Wheelâ„¢

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