Published online Jan 26, 2014. doi: 10.4252/wjsc.v6.i1.1
Revised: November 11, 2013
Accepted: December 9, 2013
Published online: January 26, 2014
Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are promising sources for hematopoietic cells due to their unlimited growth capacity and the pluripotency. Dendritic cells (DCs), the unique immune cells in the hematopoietic system, can be loaded with tumor specific antigen and used as vaccine for cancer immunotherapy. While autologous DCs from peripheral blood are limited in cell number, hPSC-derived DCs provide a novel alternative cell source which has the potential for large scale production. This review summarizes recent advances in differentiating hPSCs to DCs through the intermediate stage of hematopoietic stem cells. Step-wise growth factor induction has been used to derive DCs from hPSCs either in suspension culture of embryoid bodies (EBs) or in co-culture with stromal cells. To fulfill the clinical potential of the DCs derived from hPSCs, the bioprocess needs to be scaled up to produce a large number of cells economically under tight quality control. This requires the development of novel bioreactor systems combining guided EB-based differentiation with engineered culture environment. Hence, recent progress in using bioreactors for hPSC lineage-specific differentiation is reviewed. In particular, the potential scale up strategies for the multistage DC differentiation and the effect of shear stress on hPSC differentiation in bioreactors are discussed in detail.
Core tip: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are promising sources for hematopoietic cells. This review summarizes recent advances in differentiating hESCs and hiPSCs to dendritic cells (DCs), which are unique immune cells in the hematopoietic system and can be loaded with tumor specific antigen and used as vaccine for cancer immunotherapy. While autologous DCs from peripheral blood are limited in number, human PSC (hPSC)-derived DCs provide a novel alternative cell source for clinical application. Different strategies and effects of shear stress on large-scale production of hPSC-derived DCs in bioreactors are also discussed.