scholarly journals A unique population of bone marrow cells migrates to skeletal muscle via hepatocyte growth factor/c-met axis

2005 ◽  
Vol 118 (19) ◽  
pp. 4343-4352 ◽  
Author(s):  
M. Rosu-Myles
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Bone Marrow Cells ◽  
Factor C ◽  
Hepatocyte Growth ◽  
Marrow Cells

Hepatocyte Growth Factor Induces Differentiation of Adult Rat Bone Marrow Cells into a Hepatocyte Lineage in Vitro

2000 ◽  
Vol 279 (2) ◽  
pp. 500-504 ◽  
Author(s):  
Seh-Hoon Oh ◽  
Masahiro Miyazaki ◽  
Hirosuke Kouchi ◽  
Yusuke Inoue ◽  
Masakiyo Sakaguchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Bone Marrow Cells ◽  
Adult Rat ◽  
Hepatocyte Growth ◽  
Rat Bone ◽  
Marrow Cells

scholarly journals Role of Hepatocyte Growth Factor in Endothelial-Dependent Hematopoietic Stem Cell Regeneration

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4369-4369
Author(s):  
Derek K Zachman ◽  
Devorah C Goldman ◽  
Kimberly L Hamlin ◽  
Chandan Guha ◽  
William H. Fleming
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Conditioned Media ◽  
Cell Regeneration ◽  
Hematopoietic Stem ◽  
Hepatocyte Growth

Abstract Hematopoiesis is tightly regulated by the niche and highly sensitive to a variety of genotoxic stressors. The mechanisms responsible for the repair and regeneration of hematopoietic stem cells (HSCs) are poorly understood. Endothelial cells (ECs) are an essential component of the bone marrow microenvironment that provide regenerative signals for HSCs after injury; however, the identity of these signals remain largely unknown. We utilized RNA sequencing and a bioinformatics approach to identify hepatocyte growth factor (HGF) as an endothelial-derived mediator of HSC regeneration. HGF gene expression was 7.6-fold higher in arterial-derived ECs (HAEC) that regenerate functional long-term HSCs (CD150+LineageloSca1+Kit+ cells; CD150+LSK cells) compared to venous ECs (HUVEC) that support only hematopoietic progenitors. Furthermore, the HSC-supportive HAECs secreted up to 25 pg/mL HGF into conditioned media, whereas HGF was undetectable in media conditioned by HUVEC. To directly test the role of HGF in HSC regeneration, we supplemented co-cultures of irradiated bone marrow cells and primary ECs with recombinant HGF. Addition of HGF was sufficient to augment CD150+LSK cell regeneration up to 20-fold by HUVEC. This effect was abolished by treatment with the Met-specific small molecular inhibitor, PF04217903. Importantly, neither the addition of HGF alone to irradiated hematopoietic cells nor spiking HUVEC-conditioned media with HGF improved HSC regeneration in the absence of an EC monolayer. Together, these results indicate that HGF activates a signaling loop in ECs that supports HSC regeneration. Disclosures No relevant conflicts of interest to declare.

Abstract 1340: Disruption of a Hepatocyte Growth Factor/c-Met Receptor Autocrine Loop Severely Impairs the Potency of Pluripotent Adipose Stromal Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Liying Cai ◽  
Brian H Johnstone ◽  
Zhong Liang ◽  
Dmitry Traktuev ◽  
Todd G Cook ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Rank Order ◽  
Residual Activity ◽  
Autocrine Loop ◽  
Major Mode ◽  
Factor C ◽  
Hepatocyte Growth

Background Paracrine stimulation of endogenous repair, rather than direct tissue regeneration, is increasingly accepted as a major mode of therapeutic stem and progenitor cell action; yet, this principle has not been fully established in vivo . Adipose-derived stem cells (ASCs) secrete many factors and promote reperfusion and tissue repair in ischemia models. RNA interference was used to silence the expression of the abundant protein, hepatocyte growth factor (HGF), to determine its contribution to ASC potency in vivo . Methods and Results Dual-cassette lentiviral vectors, expressing GFP and either a small hairpin RNA (shRNA) specific for HGF mRNA (shHGF) or a control sequence (shCtrl), were used to stably transduce ASCs (ASC-shHGF or ASC-shCtrl). ASC-shHGF secreted 5-fold less HGF, which resulted in a reduced ability of these cells to promote survival, proliferation and migration of mature and progenitor endothelial cells in vitro ( p <0.01). HGF knockdown also severely impaired the ability of ASCs to promote reperfusion in a mouse hindlimb ischemia model. Perfusion of the ischemic leg at 15 d in mice treated with ASC-Ctrl was 84±4%, compared to only 69±5% for ASC-shHGF ( p <0.05). Even so, ASC-shHGF retained residual activity as indicated by greater reperfusion ( p <0.05) than with saline treatment (58±6%). Capillary densities in ischemic tissues from each group followed a similar rank order (ASC-Ctrl>ASC-shHGF>saline) ( p <0.05 between each group). While there was no difference in total GFP + cells in ischemic limbs at 5 d after infusion, indicating similar homing potentials, 3-fold fewer ASC-shHGF were present in ischemic tissues at 15 d compared to ASC-shCtrl ( p <0.01). This was accompanied by an increase in TUNEL-positive ASC-shHGF cells (61 ± 0.1%) compared to ASC-Ctrl (41% ± 3.2%) in ischemic tissues at 5 d ( p <0.01); suggesting that attenuated potency of ASC-shHGF was related to reduced survival in ischemic tissues. Conclusions These results indicate that secretion of HGF is critically important for ASC potency. In addition to promoting endogenous repair, the data suggest that an important effect of HGF is autocrine promotion of ASC survival in ischemic tissue. Enhanced donor cell survival is an important goal for increasing the efficacy of cell therapy.

scholarly journals Hepatocyte Growth Factor Is Constitutively Produced by Human Bone Marrow Stromal Cells and Indirectly Promotes Hematopoiesis

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1560-1565 ◽  
Author(s):  
Kenji Takai ◽  
Junichi Hara ◽  
Kunio Matsumoto ◽  
Gaku Hosoi ◽  
Yuko Osugi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Gm Csf ◽  
Tumor Growth Factor ◽  
Cd34 Cells ◽  
Factor Α ◽  
Hepatocyte Growth

Bone marrow (BM) stromal cells are required for normal hematopoiesis. A number of soluble factors secreted by these cells that mediate hematopoiesis have been characterized. However, the mechanism of hematopoiesis cannot be explained solely by these known factors, and the existence of other, still unknown stromal factors has been postulated. We showed that hepatocyte growth factor (HGF ) is one such cytokine produced by human BM stromal cells. BM stromal cells were shown to constitutively produce HGF and also to express the c-MET/HGF receptor. The production of HGF was enhanced by addition of heparin and phorbol ester. Dexamethasone and tumor growth factor-β (TGF-β) inhibited the production of HGF. Interleukin-1α (IL-1α) tumor necrosis factor-α (TNF-α), and N6,2′-o-dibutyryl-adenosine-3′:5′-cyclic monophosphate (dbc-AMP) showed no obvious influence on HGF production. Western blot analysis of HGF derived from BM stromal cells showed two bands at 85 and 28 kD corresponding to native and variant HGF, respectively. Addition of recombinant HGF significantly promoted the formation of burst-forming unit-erythroid (BFU-E) and colony-forming unit-granulocyte erythroid macrophage (CFU-GEM) by BM mononuclear cells in the presence of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF ), but the formation of CFU-GM was not modified. However, HGF had no effects on colony formation by purified CD34+ cells. Within BM mononuclear cells, c-MET was expressed on a proportion of cells (CD34−, CD33+, CD13+, CD14+, and CD15+), but was not found on CD34+ cells. We conclude that HGF is constitutively produced by BM stromal cells and that it enhances hematopoiesis. In addition, expression of c-MET on the stromal cells suggests the presence of an autocrine mechanism, operating through HGF, among stromal cells.

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