Dendritic cells derived from pluripotent stem cells: Potential of large scale production

Table 1 Bioreactor systems for hematopoietic differentiation from pluripotent stem cells

Bioreactor type	PSC line	Performance	Ref.
Spinner flask	hESC lines: H9 and H1	15-fold expansion in cell number compared to 4-fold in static culture; 5%-6% CD34+ CD31+ cells	Cameron et al[27]
RWV	Mouse ESC line: R1	Hematopoietic differentiation in RWV generated more Sca-1+ cells; while spinner flasks generated more c-kit+ progenitors	Fridley et al[25]
Microcarrier-based spinner flask	hESC lines: WA01 (H1), WA09 (H9), HuES3, MA09; hiPSC line: IMR90-1	DE-53 microcarriers were used. EBs were formed 10 times more efficiently compared to 2-D culture; CFUs were similar to static culture	Lu et al[67]
Perfusion bioreactor	Mouse ESC line: D3 Mouse ESC line: CCE	Perfusion promoted hematopoietic differentiation; Perfusion in 3-D fibrous scaffolds supported 2-3 fold higher cell density compared to static culture; comparable CFU percentage	Wolfe et al[77]; Li et al[24]

hESC: Human embryonic stem cell; ESC: Embryonic stem cell; EBs: Embryoid bodies; hiPSC: Human induced pluripotent stem cell; RWV: Rotary wall vessel; CFU: Colony-forming units.

Table 2 Effects of shear stress in bioreactors on pluripotent stem cells expansion and differentiation

Shear stress	Effect on pluripotency	Effect on differentiation	Ref.
Agitation in stirred bioreactors	Bioreactor-differentiated ESCs retained the ability to express pluripotent markers	EBs in bioreactors differentiated into cardiomyocytes	Shafa et al[73]
Agitation in stirred bioreactors (3 dyne/cm2vs 6 dyne/cm2)	Shear stress maintained certain pluripotent markers (e.g., Nanog, Rex-1)	Reduced spontaneous differentiation	Gareau et al[72]
Agitation in stirred bioreactors	A subpopulation of bioreactor-differentiated ESCs expressed the pluripotent markers	Differentiation into osteogenic and chondrogenic cell types	Taiani et al[74]
Agitation in stirred bioreactors (glass ball impeller, < 1.52 dyne/cm2)	Homogeneous aggregate size distribution	Cells maintained the differentiation potential into hematopoietic cells	Wang et al[79]
Rotary orbital shaking (< 2.5 dyne/cm2)	Shear stress up-regulated genes specific for endoderm and mesoderm differentiation	Spontaneous three-germ layer differentiation	Sargent et al[63]
Perfusion flow (1.5-15 dyne/cm2)	Shear stress promoted early differentiation of ESCs	Shear stress promoted hematopoietic and endothelial differentiation	Wolfe et al[77]
Agitation in microcarrier-based bioreactors	HES-2 line and hiPSC line IMR-90 were shear sensitive, showing the down-regulation of pluripotent markers	Shear stress induced spontaneous differentiation	Leung et al[76]

ESC: Embryonic stem cell; EBs: Embryoid bodies; hiPSC: Human induced pluripotent stem cell.