Functional Expression of HGF and HGF Receptor/c‐met in Adult Human Mesenchymal Stem Cells Suggests a Role in Cell Mobilization, Tissue Repair, and Wound Healing

Neuß, Sabine; Becher, Eva; Wöltje, Michael; Tietze, L.; Jahnen‐Dechent, Willi

doi:10.1634/stemcells.22-3-405

Cited by 307 publications

(258 citation statements)

References 43 publications

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“…In vivo, HGF/SF is generally produced by mesenchymal cells and activates its receptor Met, expressed in epithelial and endothelial cells, through a paracrine mode of action (Figure 2). However, Met and HGF are both expressed by mesenchymal stem cells, where HGF/SF promotes the migration and proliferation of stem cells involved in tissue repair and wound healing (Neuss et al, 2004;Forte et al, 2006), consistent with a prominent role for Met and HGF/SF in tissue repair in the adult (Michalopoulos and DeFrances, 1997;Nakamura et al, 2000;Matsumoto and Nakamura, 2001). During embryogenesis, HGF/SF and Met are essential.…”

Section: Met and Hgf/sf Elicit A Program Of Proliferative And Invasivmentioning

confidence: 72%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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The receptor for hepatocyte growth factor (HGF)/scatter factor (SF), Met, controls a program of invasive epithelial growth through the coordination of cell proliferation and survival, cell migration and epithelial morphogenesis. This process is important during embryogenesis and for organ regeneration in the adult. However, when deregulated the HGF/SF-Met signaling axis contributes to tumorigenesis and metastasis. Studies on the oncogenic activation of the Met receptor have shed light on the molecular mechanisms underlying the oncogenic activation of receptor tyrosine kinase (RTKs). More than a decade ago, work on the Met related oncogene, Tpr-Met, revealed the mechanism for activation of RTK-derived oncogenes generated following chromosomal translocation. More recently, studies on the mechanisms of downregulation of the Met RTK highlight a role for loss of downregulation in RTK oncogenic activation.

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Section: Met and Hgf/sf Elicit A Program Of Proliferative And Invasivmentioning

confidence: 72%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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“…• Hepatocyte growth factor (HGF), a multifunctional cytokine originally characterized as a mitogen for hepatocytes, and its cognate receptor HGFR/c-met, are constitutively expressed in MSCs, where HGF signaling stimulates the chemotactic migration and recruitment of MSCs in vitro (Neuss et al, 2004;Son et al, 2006) (Table 2).…”

Section: Homing and Extravasationmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

110

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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“…HGF is a pleiotropic cytokine 2 that is produced and proteolytically activated during tissue damage, 3,4 including ischemia of the heart 5 and brain. 6 It exerts its effects via interaction with the MET receptor.…”

mentioning

confidence: 99%

“…8,9 It is cardioprotective and neuroprotective and contributes to tissue regeneration in other organs as well, partially due to anti-apoptotic, pro-angiogenic and mitogenic activities. 2,[10][11][12] Moreover, HGF attracts stem and progenitor cells, including cardiac stem cells, 13 neuronal stem cells, 14 endothelial progenitor cells 15 and mesenchymal stem cells (MSC), 4,9 which probably contributes to its tissue protective and regenerative effects.…”

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confidence: 99%

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

et al. 2015

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Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.

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Functional Expression of HGF and HGF Receptor/c‐met in Adult Human Mesenchymal Stem Cells Suggests a Role in Cell Mobilization, Tissue Repair, and Wound Healing

Abstract: ABSTRACT

Cited by 307 publications

References 43 publications

From Tpr-Met to Met, tumorigenesis and tubes

From Tpr-Met to Met, tumorigenesis and tubes

How stem cells speak with host immune cells in inflammatory brain diseases

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

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