Table 3.

Bioreactor systems for MSC-EV production

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