Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

Valente, Sabrina; Ciavarella, Carmen; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andréa; Pasquinelli, Gianandrea

doi:10.1155/2016/3232859

Cited by 17 publications

(12 citation statements)

References 39 publications

(61 reference statements)

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“…The migration potential of MSCs are suppressed under hyperglycemia mainly due to its suppressive effect on the expression and secretion of the various wound healing‐related factors; and this is another causative reason for the decreased therapeutic effect of MSCs under hyperglycemia . As described above, salidroside increased the mRNA expression levels of FGF2 and HGF, both of which are known to be essential factors for MSCs migration .Conform with this, our results also demonstrated that knocking down FGF2 (Supporting Information Fig. S3A–S3C) and HGF (Supporting Information Fig.…”

Section: Resultssupporting

confidence: 85%

“…HGF has been reported to enhance wound healing by promoting keratinocytes at the wound site . Furthermore, previous studies also showed that HGF treatment could also enhanced MSCs migration , and that combination therapy using FGF2 and HGF could promote wound healing in a mouse model . HGF could also exert antiapoptotic activity as it induces phosphorylation of c‐Met, which binds and activates PI3K and further promotes cell survival .…”

Section: Discussionmentioning

confidence: 99%

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Salidroside-Pretreated Mesenchymal Stem Cells Enhance Diabetic Wound Healing by Promoting Paracrine Function and Survival of Mesenchymal Stem Cells Under Hyperglycemia

Ariyanti

Zhang

Marcelina

et al. 2019

Stem Cells Translational Medicine

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Systemic abnormalities cause several complications in diabetes patients. Impaired wound healing is a serious complication that leads to severe foot ulcer and amputation. Mesenchymal stem cells (MSCs) have been considered a promising strategy for promoting wound healing due to their paracrine function. However, their poor survival after transplantation limits their therapeutic effect and applications. Salidroside, a glucopyranoside, has been reported to exert cytoprotective effects. Our previous study revealed that salidroside could promote the paracrine function of skeletal muscle cells. However, whether salidroside could improve MSCs survival under hyperglycemic condition and, subsequently, promote wound healing in diabetic model mice remains unknown. Here, we found that salidroside pretreatment effectively reversed the hyperglycemia‐induced suppression of the expression of crucial wound healing factors in MSCs, such as heme oxygenase‐1 (HO‐1), fibroblast growth factor 2 (FGF2), and hepatocyte growth factor (HGF). Salidroside pretreatment also suppressed the hyperglycemia‐induced intracellular reactive oxygen species (ROS) levels in MSCs, thereby lowering the apoptosis rate and enhancing MSCs survival rate. Furthermore, salidroside improved the MSCs migration potential that was impaired under hyperglycemia. in vivo experiments revealed that salidroside pretreatment prior to transplantation significantly enhanced the effect of MSCs in promoting wound closure in diabetic mice. Collectively, our results suggest that pretreatment with salidroside could be an effective strategy to enhance the survival rate and the therapeutic effect of MSCs. Thus, our article suggested a novel, potential MSC‐based strategy for diabetic wound healing. Stem Cells Translational Medicine 2019;8:404–414

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Salidroside-Pretreated Mesenchymal Stem Cells Enhance Diabetic Wound Healing by Promoting Paracrine Function and Survival of Mesenchymal Stem Cells Under Hyperglycemia

Ariyanti

Zhang

Marcelina

et al. 2019

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that c-Met enhances the ability of MSCs to migrate to the sites of injury after acute liver failure [17]. The same phenomenon has been observed in vascular ulcers; the activity of HGF and c-Met in arterial MSCs supplements cell migration, angiogenesis, and vasculogenesis [18]. Moreover, pretreatment of MSCs with HGF enhances their ability to respond to ischemia by promoting cell migration and cytokine secretion, which augment regeneration and wound healing [19].…”

Section: Introductionmentioning

confidence: 74%

C-Met-Activated Mesenchymal Stem Cells Rescue Ischemic Damage via Interaction with Cellular Prion Protein

Han

Yun

Lee

et al. 2018

Cell Physiol Biochem

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Background/Aims: Stem cell transplantation has emerged as a promising therapeutic strategy, but the exact mechanisms by which stem cells exposed to hypoxic conditions increase the survival rate and rescue ischemic injury at the graft site are not well known. In this study, we aimed to determine if c-Met-activated mesenchymal stem cells (MSCs) pre-exposed to hypoxia promote therapeutic efficacy when transplanted to ischemic models, and whether c-Met interacts with cellular prion protein (PrP^C) present in the ischemic tissue. Methods: Western blot analysis was performed to determine the expression levels of PrP^C, C-caspase-3, and C-PARP-1, as well as the phosphorylation of Akt, p38, JNK, and BAX. A co-immunoprecipitation assay was performed to show that PrP^C binds with c-Met in vitro. An adhesion assay was performed to explore the alterations in MSCs attached to myoblasts (in vitro), and an invasion assay was performed to determine the effect on MSC invasion capacity upon interaction with myoblast-induced c-Met and PrP^C. CD31-positive capillaries and αSMA-positive arterioles in in vivo hindlimb ischemic tissue were quantified by immunofluorescence staining. The level of apoptosis in the tissue of each group was assessed by quantifying the number of C-caspase-3-positive cells. Finally, laser Doppler technology was utilized to detect the enhanced angiogenic effects in vivo. Results: We showed that hypoxic conditions increased PrP^C levels in vivo (hindlimb ischemic tissue) and in vitro (myoblasts) and increased c-Met levels in MSCs. To identify the relationship between c-Met from MSCs and PrP^C from myoblasts, we used a co-culturing system with myoblasts and MSCs pre-exposed to hypoxia. Hypoxia increased the phosphorylation of mitogen-activated protein kinases. Transplantation of hypoxia-pre-exposed MSCs to the ischemic site increased anti-apoptosis and enhanced the survival and proliferation of transplanted MSCs in a murine hindlimb model, resulting in improved functional recovery of the ischemic tissue. All the aforementioned effects were inhibited by the pretreatment of MSCs with the c-Met-neutralizing antibody Conclusion: c-Met-activated MSCs pre-exposed to hypoxia interact with PrP^C at the site of ischemic injury to increase the efficiency of MSC transplantation. Hence, our study demonstrated that c-Met is a potential target for MSC-based therapies.

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“…Recent years, some reports illustrated the potential clinical usage of growth factors in wound healing and tissue repair. HGF is one of the potential growth factors which participate in the whole process of wound healing [6,22]. While the function of HGF in cancer development and epithelial cell activities has been well discussed, the role of HGF signaling in inflammation and wound healing is gaining increasing focus.…”

Section: Discussionmentioning

confidence: 99%

“…HGF treatment can decrease the Lymphocytes of the spleen in mice model [16]. Overexpression of HGF was tested as a way to enhance connective inflammation repair rather than re-epithelialization of wounds [22,29]. In terms of the effect of HGF on circulating immune cells and CD45+ T cells in connective tissue of oral ulcers, HGF failed to induce a significant decrease in circulating immune cell numbers or tissue T cells compared with WT mice.…”

Section: Recent Studies Have Described the Indispensable Contributionmentioning

confidence: 99%

Anti-inflammatory effect of HGF responses to traumatic oral ulcers using an HGF-Tg mouse model

Wang

Yan

Tang

et al. 2020

Preprint

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Background: Hepatocyte growth factor (HGF) has been implicated in inhibiting diverse types of inflammation and promoting wound healing. In this study, we demonstrate the anti-inflammatory effect of HGF on traumatic ulcer of oral mucosa using HGF overexpression transgenic C57BL/6 (HGF-Tg) mice. In total, 29 C57BL/6 (WT) and 29 HGF-Tg mice were used in this study. Traumatic ulcer of left mucosa was performed by abrasion using a n 15 surgery knife. Ulcer tissues and serum samples were collected on 5 th day, histological score, expression of inflammatory cells and serum cytokines expression were measured and analyzed. Results: There existed statistical significant difference in connective Ly6G positive cells and NF-кB positive expression, HGF-Tg mice showed lower number of positive cells ( p =0.048, p =0.020 ). Eotaxin ( t -test, p =0.002), MIP-1gamma ( t -test, p =0.011), BLC ( t -test, p =0.03),Eotaxin-2 ( t -test, p =0.027), RANTES ( t -test, p =0.038), Lix ( t -test, p =0.04) and IL-3 ( t -test, p =0.047) had statistical significance higher expression in HGF-Tg mice. No significant difference of blood T cells ( p =0.998), Neutrophils ( p =0.331),Macrophages ( p =0.470) and CD4+/CD8+ ratio ( p =0.451) between HGF-Tg and WT group. Conclusions: We observed that HGF-Tg animals presented less Ly6G-positive neutrophil infiltration, higher levels of circulating cytokines and less NF- к B expression in connective tissue, with a positive effect on the healing of oral traumatic ulcers. Key words: HGF, oral ulcer, cytokine, inflammation

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Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

Cited by 17 publications

References 39 publications

Salidroside-Pretreated Mesenchymal Stem Cells Enhance Diabetic Wound Healing by Promoting Paracrine Function and Survival of Mesenchymal Stem Cells Under Hyperglycemia

Salidroside-Pretreated Mesenchymal Stem Cells Enhance Diabetic Wound Healing by Promoting Paracrine Function and Survival of Mesenchymal Stem Cells Under Hyperglycemia

C-Met-Activated Mesenchymal Stem Cells Rescue Ischemic Damage via Interaction with Cellular Prion Protein

Anti-inflammatory effect of HGF responses to traumatic oral ulcers using an HGF-Tg mouse model

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