PMID- 21106069
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1476-8518 (Electronic)
IS  - 1476-8518 (Linking)
VI  - 8
DP  - 2010 Nov 24
TI  - Ex vivo development, expansion and in vivo analysis of a novel lineage of 
      dendritic cells from hematopoietic stem cells.
PG  - 8
LID - 10.1186/1476-8518-8-8 [doi]
AB  - Dendritic cells (DCs) play a key role in innate and adaptive immunity but the 
      access to sufficient amount of DCs for basic and translational research has been 
      limited.We established a novel ex vivo system to develop and expand DCs from 
      hematopoietic stem/progenitor cells (HPCs). Both human and mouse HPCs were 
      expanded first in feeder culture supplemented with c-Kit ligand (KL, stem cell 
      factor, steel factor or CD117 ligand), Flt3 ligand (fms-like tyrosine kinase 3, 
      Flt3L, FL), thrombopoietin (TPO), IL-3, IL-6, and basic fibroblast growth factor 
      (bFGF), and then in a second feeder culture ectopically expressing all above 
      growth factors plus GM-CSF and IL-15.In the dual culture system, CD34+ HPCs 
      differentiated toward DC progenitors (DCPs), which expanded more than five orders 
      of magnitude. The DCPs showed myeloid DC surface phenotype with up-regulation of 
      transcription factors PU.1 and Id2, and DC-related factors homeostatic chemokine 
      ligand 17 (CCL17) and beta-chemokine receptor 6 (CCR6). Multiplex ELISA array and 
      cDNA microarray analyses revealed that the DCPs shared some features of IL-4 and 
      IL-15 DCs but displayed a pronounced proinflammatory phenotype. DCP-derived DCs 
      showed antigen-uptake and immune activation functions analogous to that of the 
      peripheral blood-derived DCs. Furthermore, bone marrow HPC-derived DCP vaccines 
      of tumor-bearing mice suppressed tumor growth in vivo.This novel approach of 
      generating DCP-DCs, which are different from known IL-4 and IL-15 DCs, overcomes 
      both quantitative and qualitative limitations in obtaining functional autologous 
      DCs from a small number of HPCs with great translational potential.
FAU - Han, Shuhong
AU  - Han S
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, Florida, 32610 USA. lchang@mgm.ufl.edu.
FAU - Wang, Yichen
AU  - Wang Y
FAU - Wang, Bei
AU  - Wang B
FAU - Patel, Ekta
AU  - Patel E
FAU - Okada, Starlyn
AU  - Okada S
FAU - Yang, Li-Jun
AU  - Yang LJ
FAU - Moreb, Jan S
AU  - Moreb JS
FAU - Chang, Lung-Ji
AU  - Chang LJ
LA  - eng
PT  - Journal Article
DEP - 20101124
PL  - England
TA  - J Immune Based Ther Vaccines
JT  - Journal of immune based therapies and vaccines
JID - 101152206
PMC - PMC3004889
EDAT- 2010/11/26 06:00
MHDA- 2010/11/26 06:01
PMCR- 2010/11/24
CRDT- 2010/11/26 06:00
PHST- 2010/07/23 00:00 [received]
PHST- 2010/11/24 00:00 [accepted]
PHST- 2010/11/26 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2010/11/26 06:01 [medline]
PHST- 2010/11/24 00:00 [pmc-release]
AID - 1476-8518-8-8 [pii]
AID - 10.1186/1476-8518-8-8 [doi]
PST - epublish
SO  - J Immune Based Ther Vaccines. 2010 Nov 24;8:8. doi: 10.1186/1476-8518-8-8.