PMID- 12200694
OWN - NLM
STAT- MEDLINE
DCOM- 20020926
LR  - 20130304
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 16
IP  - 9
DP  - 2002 Sep
TI  - Stromal cells from murine embryonic aorta-gonad-mesonephros region, liver and gut 
      mesentery expand human umbilical cord blood-derived CAFC(week6) in extended 
      long-term cultures.
PG  - 1782-90
AB  - The first definitive long-term repopulating hematopoietic stem cells (HSCs) 
      emerge from and undergo rapid expansion in the embryonic aorta-gonad-mesonephros 
      (AGM) region. To investigate the presumptive unique characteristics of the 
      embryonic hematopoietic microenvironment and its surrounding tissues, we have 
      generated stromal clones from subdissected day 10 and day 11 AGMs, embryonic 
      livers (ELs) and gut mesentery. We here examine the ability of 19 of these clones 
      to sustain extended long-term cultures (LTCs) of human CD34(+) umbilical cord 
      blood (UCB) cells in vitro. The presence of in vitro repopulating cells was 
      assessed by sustained production of progenitor cells (extended LTC-CFC) and 
      cobblestone area-forming cells (CAFC). The embryonic stromal clones differed 
      greatly in their support for human HSCs. Out of eight clones tested in the 
      absence of exogenous cytokines, only one (EL-derived) clone was able to provide 
      maintenance of HSCs. Addition of either Tpo or Flt3-L + Tpo improved the 
      long-term support of about 50% of the tested clones. Cultures on four out of 19 
      clones, ie the EL-derived clone mentioned, two urogenital-ridge (UG)-derived 
      clones and one gastrointestinal (GI)-derived clone, allowed a continuous 
      expansion of primitive CAFC and CFU-GM with over several hundred-fold more 
      CAFC(week6) produced in the 12th week of culture. This expansion was considerably 
      higher than that found with the FBMD-1 cell line, which is appreciated by many 
      investigators for its support of human HSCs, under comparable conditions. This 
      stromal cell panel derived from the embryonic regions may be a powerful tool in 
      dissecting the factors mediating stromal support for maintenance and expansion of 
      HSCs.
FAU - Kusadasi, N
AU  - Kusadasi N
AD  - Institute of Hematology, Erasmus Medical Center Rotterdam, The Netherlands.
FAU - Oostendorp, R A J
AU  - Oostendorp RA
FAU - Koevoet, W J L M
AU  - Koevoet WJ
FAU - Dzierzak, E A
AU  - Dzierzak EA
FAU - Ploemacher, R E
AU  - Ploemacher RE
LA  - eng
GR  - R01 DK51077/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD34)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Antigens, CD34/metabolism
MH  - Aorta/embryology
MH  - Cell Lineage
MH  - Cell Separation
MH  - Clone Cells/cytology
MH  - Coculture Techniques
MH  - Colony-Forming Units Assay
MH  - Cytokines/metabolism
MH  - Digestive System/embryology
MH  - Embryo, Mammalian/*cytology
MH  - Fetal Blood/*cytology
MH  - Gonads/embryology
MH  - Graft Survival
MH  - Hematopoiesis
MH  - Humans
MH  - Liver/embryology
MH  - Mesentery/embryology
MH  - Mesonephros/embryology
MH  - Mice
MH  - Mice, Transgenic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cells/chemistry/*cytology/drug effects
MH  - Stromal Cells/*cytology/metabolism
EDAT- 2002/08/30 10:00
MHDA- 2002/09/27 06:00
CRDT- 2002/08/30 10:00
PHST- 2002/02/01 00:00 [received]
PHST- 2002/04/16 00:00 [accepted]
PHST- 2002/08/30 10:00 [pubmed]
PHST- 2002/09/27 06:00 [medline]
PHST- 2002/08/30 10:00 [entrez]
AID - 10.1038/sj.leu.2402615 [doi]
PST - ppublish
SO  - Leukemia. 2002 Sep;16(9):1782-90. doi: 10.1038/sj.leu.2402615.