scholarly journals Intrathecal Injection of Hepatocyte Growth Factor Gene-modified Marrow Stromal Cells Attenuates Neurologic Injury Induced by Transient Spinal Cord Ischemia in Rabbits

2010 ◽  
Vol 113 (5) ◽  
pp. 1109-1117 ◽  
Author(s):  
Enyi Shi ◽  
Xiaojing Jiang ◽  
Lingling Wang ◽  
Satoshi Akuzawa ◽  
Yoshiki Nakajima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Motor Neurons ◽  
Stromal Cells ◽  
Spinal Cord Ischemia ◽  
Intrathecal Injection ◽  
Marrow Stromal Cells ◽  
Infrarenal Aorta ◽  
Hepatocyte Growth

Background Our previous studies showed that transfer of hepatocyte growth factor (HGF) gene or transplantation of marrow stromal cells (MSCs) remarkably attenuated neurologic injuries after spinal cord ischemia. We sought to investigate a novel neuroprotective strategy of transplantation of human HGF gene-modified MSCs on ischemic spinal cords. Methods Human HGF gene was transferred into MSCs in vitro. The HGF gene-modified MSCs were transplanted by means of intrathecal injection. Two days later, spinal cord ischemia was induced by occlusion of the infrarenal aorta with a balloon catheter for 40 or 50 min. Hind-limb motor function was assessed during a 14-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Human HGF was detected in the cerebrospinal fluid from 2 to 16 days after transplantation of HGF gene-modified MSCs. Compared with the controls, transplantation of HGF gene-modified MSCs or MSCs alone significantly improved the Tarlov scores 1, 2, 7, and 14 days after spinal cord ischemia of 40 or 50 min (P < 0.01, respectively) and increased the number of intact motor neurons in the lumbar spinal cord (P < 0.01, respectively). When the ischemic period was extended to 50 min, the Tarlov scores and the number of intact motor neurons of rabbits transplanted with HGF gene-modified MSCs were markedly higher than those of the rabbits transplanted with MSCs only (P < 0.05, respectively). Conclusions Transplantation of HGF gene-modified MSCs induces powerful neuroprotection on spinal cords against ischemia-reperfusion injury and is more therapeutically efficient than transplantation of MSCs only.

Intrathecal Injection of Bone Marrow Stromal Cells Attenuates Neurologic Injury After Spinal Cord Ischemia

2006 ◽  
Vol 81 (6) ◽  
pp. 2227-2234 ◽  
Author(s):  
Enyi Shi ◽  
Teruhisa Kazui ◽  
Xiaojing Jiang ◽  
Naoki Washiyama ◽  
Katsushi Yamashita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Spinal Cord Ischemia ◽  
Intrathecal Injection ◽  
Marrow Stromal Cells ◽  
Neurologic Injury

The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axons

Development ◽  
2000 ◽  
Vol 127 (8) ◽  
pp. 1751-1766 ◽  
Author(s):  
A. Caton ◽  
A. Hacker ◽  
A. Naeem ◽  
J. Livet ◽  
F. Maina ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Motor Neurons ◽  
Branchial Arch ◽  
Sensory Ganglia ◽  
Motor Axons ◽  
Collagen Gels ◽  
Branchial Arches ◽  
Growth Promoting ◽  
Hepatocyte Growth

During development, cranial motor neurons extend their axons along distinct pathways into the periphery. For example, branchiomotor axons extend dorsally to leave the hindbrain via large dorsal exit points. They then grow in association with sensory ganglia, to their targets, the muscles of the branchial arches. We have investigated the possibility that pathway tissues might secrete diffusible chemorepellents or chemoattractants that guide cranial motor axons, using co-cultures in collagen gels. We found that explants of dorsal neural tube or hindbrain roof plate chemorepelled cranial motor axons, while explants of cranial sensory ganglia were weakly chemoattractive. Explants of branchial arch mesenchyme were strongly growth-promoting and chemoattractive for cranial motor axons. Enhanced and oriented axon outgrowth was also elicited by beads loaded with Hepatocyte Growth Factor (HGF); antibodies to this protein largely blocked the outgrowth and orientation effects of the branchial arch on motor axons. HGF was expressed in the branchial arches, whilst Met, which encodes an HGF receptor, was expressed by subpopulations of cranial motor neurons. Mice with targetted disruptions of HGF or Met showed defects in the navigation of hypoglossal motor axons into the branchial region. Branchial arch tissue may thus act as a target-derived factor that guides motor axons during development. This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies.

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.

scholarly journals Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury

2019 ◽  
Vol 20 (23) ◽  
pp. 6078 ◽  
Author(s):  
Kentaro Yamane ◽  
Haruo Misawa ◽  
Tomoyuki Takigawa ◽  
Yoshihiro Ito ◽  
Toshifumi Ozaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Stem Cell Differentiation ◽  
Neural Regeneration ◽  
Therapeutic Effects ◽  
Positive Effects ◽  
Cord Injury ◽  
Hepatocyte Growth

Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy.

Effects of Intrathecal Injection of the Conditioned Medium from Bone Marrow Stromal Cells on Spinal Cord Injury in Rats

2018 ◽  
Vol 35 (3) ◽  
pp. 521-532 ◽  
Author(s):  
Kenji Kanekiyo ◽  
Tamami Wakabayashi ◽  
Norihiko Nakano ◽  
Yoshihiro Yamada ◽  
Masahiro Tamachi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Conditioned Medium ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Intrathecal Injection ◽  
Marrow Stromal Cells ◽  
Cord Injury

scholarly journals Hepatocyte Growth Factor/Scatter Factor Is an Axonal Chemoattractant and a Neurotrophic Factor for Spinal Motor Neurons

Neuron ◽  
1996 ◽  
Vol 17 (6) ◽  
pp. 1157-1172 ◽  
Author(s):  
Allen Ebens ◽  
Katja Brose ◽  
E.David Leonardo ◽  
M.Gartz Hanson Jr ◽  
Friedhelm Bladt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Motor Neurons ◽  
Neurotrophic Factor ◽  
Scatter Factor ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Hepatocyte Growth
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