Mesenchymal Stromal Cells: From Discovery to Manufacturing and Commercialization

Table 1

MSC cell expansion in monolayer culture systems and bioreactors.

Type	Culture medium	Working volume (mL)	MSC source/culture conditions	Time in culture (days)	Fold increase	Final cell number	Reference
10-layer HYPER flasks (Corning)	α-MEM + 15% AB human serum	560	UCM MSC	11	13	45 × 10^6 cells	[39]
Roller bottles (Greiner)	α-MEM + 15% AB human serum	200	UCM MSC	6	7.0	29 × 10^6 cells	[39]
3 L stirred tank bioreactor (EMD Millipore, Mobius)	DMEM + 10% FBS	2000	BM and AT MSC on collagen-coated microcarriers	5	5.2	n.r.	[49]
1 L bioreactor (Sartorius Biostat B-DCU)	DMEM + 10% FBS	1000	BM MSC cultivated on Cytodex-3 microcarrier	8	12	600 × 10^6 cells	[50]
3 L stirred tank bioreactor (Merck-Millipore, Mobius™ CellReady 3L)	DMEM + 10% FBS	2400	BM MSC cultured on collagen-coated SoloHill microcarriers	12	62	270 × 10^6 cells/L	[51]
5 L stirred tank bioreactor (Sartorius, Biostat B Plus)	DMEM + 10% FBS	2500	BM MSC cultivated on Plastic P-102L microcarrier	12	>6	420 × 10^6 cells	[52]
1.3 L stirred tank bioreactor (New Brunswick, Bioflo)	StemPro® MSC SFM XenoFree	800	BM and AT MSC cultivated on nonporous plastic microcarrier	7	n.r.	110 × 10^6 cells for BM MSC and 45 × 10^6 cells for AT MSC	[53]
2 L stirred tank bioreactor (UniVessel SU, Sartorius)	Serum-reduced (5%) medium	2000	AT MSC cultivated on Pronectin F microcarrier	7	27	540 × 10^6 cells	[54]
2 L stirred tank bioreactor (Biostat B-DCU, Sartorius)	α-MEM + 10% FBS	800	Fetal BM MSC cultivated on Cytodex-3	7	16	0.46 × 10^5 cells/cm^2	[55]
2.5 L stirred tank bioreactor (New Brunswich, Celligen 310)	StemPro MSC SFM XenoFree	800	UCM MSC cultivated in Cultispher-S microcarrier	5	5.3	110 × 10^6 cells	[56]
2.5 L stirred tank bioreactor (New Brunswich, Celligen 310)	α-MEM + 15% AB human serum	800	UCM MSC cultivated on Plastic P-102L microcarrier	7	8.9	79 × 10^6 cells	[39]
2 L stirred tank bioreactor (Sartorius, UniVessel® SU bioreactor)	Mesencult™-XF	1000	BM and AT MSC cultivated on Synthemax® II microcarrier	7	14 for BM MSC and 16 for AT MSC	680 × 10^6 cells for BM MSC and 820 × 10^6 cells for AT MSC	[57]
Hollow fiber (Quantum, Terumo BCT)	DMEM + 10% Human Platelet Lysate	n.r.	BM MSC	13	10–20	2–58 × 10^6 cells	[58]
Hollow fiber (Quantum, Terumo BCT)	DMEM + 10% FBS	n.r.	BM MSC	7	5.5–14	110–276 × 10^6 cells	[59]
Hollow fiber (Quantum, Terumo BCT)	α-MEM + 10% FBS	n.r.	AT MSC	17	4.7	99 × 10^6 cells	[60]
Hollow fiber (Quantum, Terumo BCT)	DMEM + 10% FBS	n.r.	PD MSC	8	16–22	316–444 × 10^6 cells	[61]
Rocking bioreactor (GE Healthcare)	LGDMEM + 20% FBS	2000	Pl MSC cultivated on Cytodex-3 and Cultispher-S microcarrier	7	10 for Cytodex-3; 15 for Cultispher-S	n.r.	[62]
Fixed-bed bioreactor (New Brunswich)	α-MEM + 10% FBS	500	UCM MSC in a Fibrastage® bioreactor with FibraCel disks	7	7	420 × 10^6 cells	[63]
Fixed-bed bioreactor (New Brunswich, Celligen 310)	α-MEM + 10% FBS	2500	BM MSC	9	9.2	10–92 × 10^6 cells	[64]

n.r.: not reported; FBS: fetal bovine serum; UCM MSC: mesenchymal stem cell derived from umbilical cord; BM MSC: mesenchymal stem cell derived from bone marrow; AT MSC: mesenchymal stem cell derived from adipose tissue; PD MSC: mesenchymal stem cell derived from periosteum; Pl MSC: mesenchymal stem cell derived from placenta.