| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
,,
,¶
* Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706;
Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715;
WiCell Research Institute, Madison, WI 53707;
Department of Anatomy, University of Wisconsin Medical School, Madison, WI 53706; and
¶ Genome Center of Wisconsin, University of Wisconsin, Madison, WI 53706
We have established a system for directed differentiation of human embryonic stem (hES) cells into myeloid dendritic cells (DCs). As a first step, we induced hemopoietic differentiation by coculture of hES cells with OP9 stromal cells, and then, expanded myeloid cells with GM-CSF using a feeder-free culture system. Myeloid cells had a CD4+CD11b+CD11c+CD16+CD123lowHLA-DR– phenotype, expressed myeloperoxidase, and included a population of M-CSFR+ monocyte-lineage committed cells. Further culture of myeloid cells in serum-free medium with GM-CSF and IL-4 generated cells that had typical dendritic morphology; expressed high levels of MHC class I and II molecules, CD1a, CD11c, CD80, CD86, DC-SIGN, and CD40; and were capable of Ag processing, triggering naive T cells in MLR, and presenting Ags to specific T cell clones through the MHC class I pathway. Incubation of DCs with A23187 calcium ionophore for 48 h induced an expression of mature DC markers CD83 and fascin. The combination of GM-CSF with IL-4 provided the best conditions for DC differentiation. DCs obtained with GM-CSF and TNF-
coexpressed a high level of CD14, and had low stimulatory capacity in MLR. These data clearly demonstrate that hES cells can be used as a novel and unique source of hemopoietic and DC precursors as well as DCs at different stages of maturation to address essential questions of DC development and biology. In addition, because ES cells can be expanded without limit, they can be seen as a potential scalable source of cells for DC vaccines or DC-mediated induction of immune tolerance.
This article has been cited by other articles:
|
|
 |
|
  S. Senju, H. Suemori, H. Zembutsu, Y. Uemura, S. Hirata, D. Fukuma, H. Matsuyoshi, M. Shimomura, M. Haruta, S. Fukushima, et al. Genetically Manipulated Human Embryonic Stem Cell-Derived Dendritic Cells with Immune Regulatory Function Stem Cells, November 1, 2007; 25(11): 2720 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tian, S. Grimaldo, M. Fugita, J. Cutts, N. L. Vujanovic, and L.-Y. Li The Endothelial Cell-Produced Antiangiogenic Cytokine Vascular Endothelial Growth Inhibitor Induces Dendritic Cell Maturation J. Immunol., September 15, 2007; 179(6): 3742 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Antignani and R. J. Youle The Cytokine, Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF), Can Deliver Bcl-XL as an Extracellular Fusion Protein to Protect Cells from Apoptosis and Retain Differentiation Induction J. Biol. Chem., April 13, 2007; 282(15): 11246 - 11254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bhatia Hematopoietic Development from Human Embryonic Stem Cells Hematology, January 1, 2007; 2007(1): 11 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Galic, S. G. Kitchen, A. Kacena, A. Subramanian, B. Burke, R. Cortado, and J. A. Zack From the Cover: T lineage differentiation from human embryonic stem cells PNAS, August 1, 2006; 103(31): 11742 - 11747. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
