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World J Stem Cells. Jan 26, 2014; 6(1): 1-10
Published online Jan 26, 2014. doi: 10.4252/wjsc.v6.i1.1
Dendritic cells derived from pluripotent stem cells: Potential of large scale production
Yan Li, Meimei Liu, Shang-Tian Yang
Yan Li, Department of Chemical and Biomedical Engineering, Florida Agricultural and Mechanical University-Florida State University College of Engineering, Florida State University, Tallahassee, FL 32310, United States
Meimei Liu, Shang-Tian Yang, William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, United States
Author contributions: Li Y prepared the original draft; Liu M contributed to writing and editing some sections in the manuscript; and Yang ST revised and finalized the manuscript.
Supported by In part by Florida State University start up fund and Florida State University Research Foundation GAP award; and the partial support from National Science Foundation, No. 1342192
Correspondence to: Shang-Tian Yang, Professor, William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Ave, Columbus, OH 43210, United States. yang.15@osu.edu
Telephone: +1-614-2926611 Fax: +1-614-2923769
Received: September 29, 2013
Revised: November 11, 2013
Accepted: December 9, 2013
Published online: January 26, 2014
Processing time: 137 Days and 4.8 Hours
Abstract

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.

Keywords: Pluripotent stem cells; Dendritic cells; Bioreactor; Hematopoietic differentiation; Large scale production

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.