<b>Hepatocyte growth factor is an attractive target for the treatment of pulmonary fibrosis</b>

Chakraborty, Sushmita; Chopra, Puneet; Hak, Anushree; Dastidar, Sunanda G.; Ray, Abhijit

doi:10.1517/13543784.2013.778972

Cited by 47 publications

(39 citation statements)

References 113 publications

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“…HGF exhibits potent cytoprotective properties in airway epithelial cells and has been used in numerous experimental and clinical applications [17,26,30,31]. However, because exogenous HGF is extremely unstable, with a half-life of 3-5 min in the circulation, it is nearly impossible to sustain a constantly high level of HGF in the circulation, even when using FIG.…”

Section: Discussionmentioning

confidence: 99%

“…Among the biological activities of HGF, its antifibrogenic effects are also widely known [17]. HGF-MSCs exhibit anti-fibrotic properties in experimental models of lung, kidney, heart, skin, and liver fibrosis [40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

“…HGF acts as an anti-fibrotic agent that protects the host against transforming growth factor beta1 (TGF-b1)-mediated pro-fibrotic effects [14,17]. HGF plays an important role in the tissue-repair process, but the sustained delivery of HGF into the injured area remains a major challenge.…”

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confidence: 99%

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Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

Zheng

et al. 2015

Stem Cells and Development

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This study was designed to investigate the effects of hepatocyte growth factor (HGF) transgenic mesenchymal stem cells (HGF-MSCs) on wound healing in the sinonasal mucosa and nasal epithelial cells (NECs). We also sought to determine whether HGF-MSCs and MSCs can migrate into the injured mucosa and differentiate into ciliated cells. Human HGF-overexpressing umbilical cord MSCs (hHGF-UCMSCs) were established, and upregulation of hHGF expression was confirmed by real-time PCR (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). To investigate the paracrine effect of human MSCs (hMSCs) on nasal epithelial repair, hMSC-and HGF-MSC-conditioned media (CM) were used in NEC proliferation assays and in an in vitro scratch-wound repair model. The in vivo sinonasal wound-healing model was established, and all enrolled rabbits were randomly assigned to four groups: the GFP-MSC group, the HGF-MSC group, the Ad-HGF group, and the surgery control group. The average decreased diameter was recorded, and the medial wall of the maxillary sinus was removed for histological analysis and scanning electron microscopy. Collagen deposition in the wound tissue was detected via Masson trichrome (M&T) staining. The distribution of MSCs and HGFMSCs was observed by immunofluorescence. MSCs improved nasal wound healing both in vivo and in vitro. HGF overexpression in MSCs augmented the curative effects. Reduced collagen deposition and transforming growth factor beta1 (TGF-b1) expression were detected in the HGF-MSC group compared with the MSC-, Ad-HGF-, and phosphate-buffered saline-treated groups based on M&T staining and ELISA. The enhanced therapeutic effects of HGF-MSCs were accompanied by decreased level of the fibrogenic cytokine TGF-b1. In addition, both HGF-MSCs and MSCs can migrate to the injured mucosa and epithelial layer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

Zheng

et al. 2015

Stem Cells and Development

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“…Previous studies have shown that the paracrine factors of MSCs have anti-apoptotic effects in vitro on cardiac cells (27,28), pancreatic β cells (29) and hepatocytes (19). BM-MSCs are known to produce several epithelial specific growth factors, including HGF and KGF (17,18), which have been proven to initiate a variety of biological responses including migration, proliferation, and morpho genesis in AECs (30)(31)(32)(33). Therefore it can be speculated that the protective roles of MSC-CM on AECs may be associated with the epithelial specific growth factors secreted by BM-MSCs and the synergistic effects of these factors.…”

Section: Discussionmentioning

confidence: 99%

Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis

Shen

Chen

Xiao

et al. 2014

Molecular Medicine Reports

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“…Hepatocyte growth factor (HGF) is a well-recognized factor that has the capacity to protect against fibrosis probably by promoting cell proliferation and survival, preventing the epithelial-mesenchymal transition, and by -its pro-angiogenic activity (Chakraborty et al, 2013). Our previous research has shown that HGF-modified MSCs (MSCs/HGF), generated by the transfection of an HGF cDNA-containing vector into MSCs, exhibit potent immunosuppressive activity (Bian et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up

Liu

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This nonrandomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10 6 cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4-and CD8-positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

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Hepatocyte growth factor is an attractive target for the treatment of pulmonary fibrosis

Cited by 47 publications

References 113 publications

Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis

Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up

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