PMID- 11276366
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20071114
IS  - 1525-8165 (Print)
IS  - 1525-8165 (Linking)
VI  - 10
IP  - 1
DP  - 2001 Feb
TI  - Immortalized multipotential mesenchymal cells and the hematopoietic 
      microenvironment.
PG  - 125-40
AB  - In an attempt to analyze the cellular and molecular basis of the capacity of bone 
      marrow stromal cells to support hematopoiesis in culture, we developed a series 
      of murine stromal cell lines from a single long-term bone marrow culture (BMC). 
      The cytokines produced by these cells were analyzed using immunohistochemical 
      techniques, ribonuclease protection assays (RPA) and RT-PCR. We examined the 
      capacity of these cloned cell lines to replace primary bone marrow-derived 
      stromal cells in long-term bone marrow cultures (LT-BMC) and sought correlations 
      between the capacity to support hematopoiesis in culture with the production of 
      known cytokines. These immortalized lines replicate many of the functions of the 
      hematopoietic microenvironment. They express cytokines known to play a role in 
      hematopoiesis. All of the lines constitutively express mRNA for PBSF (SDF-1), 
      macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF), FLT-3, 
      thrombopoietin (TPO), interleukin 7 (IL-7), leukemia inhibitory factor (LIF), 
      tumor necrosis factor-beta (TNF-beta), and interferon-gamma (IFN-gamma). Most 
      lines also express granulocyte-macrophage colony-stimulating factor (GM-CSF) and 
      G-CSF. They vary in their expression of IL-6, tumor growth factor-beta1 
      (TGF-beta1), TGF-beta2, and TNF-alpha. Growing these lines in the presence of 
      cytokines that influence hematopoiesis alters the levels of cytokine message. The 
      most striking effects were produced by TNF-alpha. In addition to the cytokine 
      mRNAs, the cell lines express factors associated with bone formation such as 
      osteoblast-specific factor-2 (OSF-2) and bone morphogenetic protein-1 (BMP-1). 
      They also express the neural cell-adhesion molecule neuropilin and neurotrophic 
      factors including nerve growth factor (NGF) and brain-derived neurotrophic factor 
      (BDNF). Several of the lines can maintain hematopoiesis in culture, as measured 
      by the continuous production of myeloid colony-forming cells (CFU-c), for months. 
      This capacity to support hematopoiesis does not correlate with any pattern of 
      cytokine expression. Several of these lines also support the growth of human 
      hematopoietic cells, and human CFU-c can be detected in the cultures in which 
      CD34(+) bone marrow cells (BMC) are cultured on murine stromal cells. No 
      correlation between the production of any of the known cytokines and the ability 
      to support murine hematopoiesis was detected. In addition, there was no 
      correlation between the capacity to support murine hematopoiesis and the capacity 
      to maintain human HSC. Despite repeated cloning, the lines remain heterogeneous 
      and are capable of producing cells with the properties of fibroblasts, 
      osteoblasts, adipocytes, and myoblasts. In addition to the cytokine mRNAs, the 
      cell lines express factors associated with bone formation such as OSF-2 and 
      BMP-1. They also express the neural cell-adhesion molecule neuropilin and 
      neurotrophic factors including NGF and BDNF.
FAU - Dormady, S P
AU  - Dormady SP
AD  - Department of Pathology and the Kaplan Comprehensive Cancer Center, New York 
      University School of Medicine, New York, NY 10016, USA.
FAU - Bashayan, O
AU  - Bashayan O
FAU - Dougherty, R
AU  - Dougherty R
FAU - Zhang, X M
AU  - Zhang XM
FAU - Basch, R S
AU  - Basch RS
LA  - eng
GR  - DK43376/DK/NIDDK NIH HHS/United States
GR  - DK49895/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Hematother Stem Cell Res
JT  - Journal of hematotherapy & stem cell research
JID - 100892915
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Culture Techniques
MH  - Cell Line/*cytology/metabolism
MH  - Cytokines/genetics
MH  - Growth Substances/genetics
MH  - *Hematopoiesis
MH  - Hematopoietic Stem Cells/cytology
MH  - Humans
MH  - Mesoderm/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - RNA, Messenger/metabolism
MH  - Stromal Cells/cytology
EDAT- 2001/03/29 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/03/29 10:00
PHST- 2001/03/29 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/03/29 10:00 [entrez]
AID - 10.1089/152581601750098372 [doi]
PST - ppublish
SO  - J Hematother Stem Cell Res. 2001 Feb;10(1):125-40. doi: 
      10.1089/152581601750098372.