scholarly journals c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chun Yue ◽  
Zi Guo ◽  
Yufang Luo ◽  
Jingjing Yuan ◽  
Xinxing Wan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Growth Factor ◽  
Wound Closure ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
And Migration ◽  
Proliferation And Migration

Objective. Mesenchymal stem cells (MSCs) are considered a promising therapy for wound healing. Here, we explored the role of c-Jun in diabetic wound healing using human umbilical cord-derived MSCs (hUC-MSCs). Methods. Freshly isolated hUC-MSCs were subjected to extensive in vitro subcultivation. The cell proliferative and migratory capacities were assessed by the Cell Counting Kit-8 and scratch assays, respectively. c-Jun expression was evaluated by RT-PCR and western blot analysis. The function of c-Jun was investigated with lentivirus transduction-based gene silencing and overexpression. Diabetes mellitus was induced in SD rats on a high-glucose/fat diet by streptozocin administration. Wounds were created on the dorsal skin. The effects of c-Jun silencing and overexpression on wound closure by hUC-MSCs were examined. Reepithelialization and angiogenesis were assessed by histological and immunohistochemical analysis, respectively. Platelet-derived growth factor A (PDGFA), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) levels were determined by western blot analysis. Results. hUC-MSCs showed gradually decreased cell proliferation, migration, and c-Jun expression during subcultivation. c-Jun silencing inhibited cell proliferation and migration, while c-Jun overexpression enhanced proliferation but not migration. Compared with untransduced hUC-MSCs, local subcutaneous injection of c-Jun-overexpressing hUC-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased PDGFA and HGF levels in wound tissues. Conclusion. c-Jun overexpression promoted hUC-MSC proliferation and migration in vitro and accelerated diabetic wound closure, reepithelization, and angiogenesis by hUC-MSCs in vivo. These beneficial effects of c-Jun overexpression in diabetic wound healing by hUC-MSCs were at least partially mediated by increased PDGFA and HGF levels in wound tissues.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

scholarly journals In Vitro Wound Healing Potential of Flavonoid C-Glycosides from Oil Palm (Elaeis guineensis Jacq.) Leaves on 3T3 Fibroblast Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 326 ◽  
Author(s):  
Mohamad Shazeli Che Zain ◽  
Soo Yee Lee ◽  
Murni Nazira Sarian ◽  
Sharida Fakurazi ◽  
Khozirah Shaari
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Oil Palm ◽  
Elaeis Guineensis ◽  
Fibroblast Cells ◽  
Crude Extracts ◽  
Elaeis Guineensis Jacq ◽  
And Migration ◽  
Proliferation And Migration

Oil palm (Elaeis guineensis Jacq.) leaves (OPL) are widely available at zero cost in Southeast Asia countries, especially in Malaysia and Indonesia due to large scale oil palm plantations. OPLs contain a large amount of flavonoids in particular flavonoid C-glycosides, which are known to possess useful biological properties including antioxidant and wound healing properties. The present study aimed at evaluating the wound healing efficacy of OPL in various solvent extracts and flavonoid enriched fractions and to determine the contribution of flavonoid C-glycosides (orientin, isoorientin, vitexin and isovitexin) using in-vitro scratch assay on 3T3 fibroblast cells. Solvent crude extracts with different polarity were screened and the most active extract was subjected to acid hydrolysis. The crude and acid hydrolysed extracts were further enriched using macroporous resins, XAD7HP. UHPLC-UV/PDA and LC-MS/MS analysis were applied for identification and confirmation of flavonoid C-glycosides. The wound healing properties comprised of cell viability, cell proliferation and cell migration were studied. Allantoin was used as a positive control to compare the efficacy among the tested samples. The results revealed all OPL crude extracts, flavonoid enriched fractions and flavonoid C-glycosides were non-toxic at concentrations below 25 µg/mL and showed better cell proliferation and migration activities at low concentrations than higher concentrations.. This study also demonstrated orientin, isoorientin, vitexin and isovitexin presented in OPL extracts and flavonoid enriched fractions stimulated proliferation and migration of 3T3 fibroblast cells. Hence, these findings may pose potential therapeutic bioactive agents for wound healing by enhancing fibroblast proliferation and migration.

scholarly journals Fibrin Glue Enhances Adipose-Derived Stromal Cell Cytokine Secretion and Survival Conferring Accelerated Diabetic Wound Healing

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ursula Hopfner ◽  
Matthias M. Aitzetmueller ◽  
Philipp Neßbach ◽  
Michael S. Hu ◽  
Hans-Guenther Machens ◽  
...  
Keyword(s):  
Wound Healing ◽  
Fibrin Glue ◽  
Stromal Cell ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Imaging System ◽  
Diabetic Wound ◽  
Diabetic Wound Healing

Introduction. Although chronic wounds are a major personal and economic burden, treatment options are still limited. Among those options, adipose-derived stromal cell- (ASC-) based therapies rank as a promising approach but are restricted by the harsh wound environment. Here we use a commercially available fibrin glue to provide a deliverable niche for ASCs in chronic wounds. Material and Methods. To investigate the in vitro effect of fibrin glue, cultivation experiments were performed and key cytokines for regeneration were quantified. By using an established murine chronic diabetic wound-healing model, we evaluated the influence of fibrin glue spray seeding on cell survival (In Vivo Imaging System, IVIS), wound healing (wound closure kinetics), and neovascularization of healed wounds (CD31 immunohistochemistry). Results. Fibrin glue seeding leads to a significantly enhanced secretion of key cytokines (SDF-1, bFGF, and MMP-2) of human ASCs in vitro. IVIS imaging showed a significantly prolonged murine ASC survival in diabetic wounds and significantly accelerated complete wound closure in the fibrin glue seeded group. CD31 immunohistochemistry revealed significantly more neovascularization in healed wounds treated with ASCs spray seeded in fibrin glue vs. ASC injected into the wound bed. Conclusion. Although several vehicles have shown to successfully act as cell carrier systems in preclinical trials, regulatory issues have prohibited clinical usage for chronic wounds. By demonstrating the ability of fibrin glue to act as a carrier vehicle for ASCs, while simultaneously enhancing cellular regenerative function and viability, this study is a proponent of clinical translation for ASC-based therapies.

scholarly journals In Vivo Biocompatibility of Electrospun Biodegradable Dual Carrier (Antibiotic + Growth Factor) in a Mouse Model—Implications for Rapid Wound Healing

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 180 ◽  
Author(s):  
Charu Dwivedi ◽  
Himanshu Pandey ◽  
Avinash C. Pandey ◽  
Sandip Patil ◽  
Pramod W. Ramteke ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Diabetic Wound ◽  
Scanning Calorimetry ◽  
Rapid Healing ◽  
Diabetic Wound Healing

Tissue engineering technologies involving growth factors have produced one of the most advanced generations of diabetic wound healing solutions. Using this approach, a nanocomposite carrier was designed using Poly(d,l-lactide-co-glycolide) (PLGA)/Gelatin polymer solutions for the simultaneous release of recombinant human epidermal growth factor (rhEGF) and gentamicin sulfate at the wound site to hasten the process of diabetic wound healing and inactivation of bacterial growth. The physicochemical characterization of the fabricated scaffolds was carried out using scanning electron microscopy (SEM) and X-ay diffraction (XRD). The scaffolds were analyzed for thermal stability using thermogravimetric analysis and differential scanning calorimetry. The porosity, biodegradability, and swelling behavior of the scaffolds was also evaluated. Encapsulation efficiency, drug loading capacity, and in vitro drug release were also investigated. Further, the bacterial inhibition percentage and detailed in vivo biocompatibility for wound healing efficiency was performed on diabetic C57BL6 mice with dorsal wounds. The scaffolds exhibited excellent wound healing and continuous proliferation of cells for 12 days. These results support the applicability of such systems in rapid healing of diabetic wounds and ulcers.

scholarly journals Wound healing promoting activity of Earthworm, Eutyphoeus gammiei (Beddard): in vitro studies on human skin keratinocyte cell line (HaCat).

2018 ◽  
Vol 8 (6) ◽  
pp. 155-158
Author(s):  
Susmita Saha ◽  
Deepjyoti Bhattacharjee ◽  
Anwesha Saha ◽  
Gahin De ◽  
Partha Saha ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Line ◽  
Key Factors ◽  
Cell Proliferation And Migration ◽  
Keratinocyte Cell Line Hacat ◽  
Keratinocyte Cell ◽  
And Migration ◽  
Proliferation And Migration

Earthworm, Eutyphoeus gammiei, homogenate (EGH) was screened for wound healing activity on human keratinocyte cell line, HaCat, by cell proliferation and migration assays. The maximum proliferation and migration of keratinocyte cells were observed at the dose of 25μg/ml. As cell proliferation and migration are key factors for wound healing, the study clearly suggests the potential role of earthworm species Eutyphoeus gammiei on wound healing. Keywords: Eutyphoeus gammiei, Keratinocyte, MTT assay, scratch assay.

scholarly journals Visfatin Promotes Wound Healing Through the Activation of ERK1/2 and JNK1/2 Pathway

2018 ◽  
Author(s):  
Byungcheol Lee ◽  
Jisun Song ◽  
Arim Lee ◽  
Daeho Cho ◽  
Tae Sung Kim
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Human Keratinocytes ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Vegf Expression ◽  
And Migration ◽  
Proliferation And Migration

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.

scholarly journals Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

2021 ◽  
Author(s):  
Qian Wei ◽  
Yaxi Wang ◽  
Kui Ma ◽  
Xiaowei Bian ◽  
Qiankun Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Background: Endothelial dysfunction caused by persistent hyperglycemia in diabetes is responsible for impaired angiogenesis in diabetic wounds. Exosomes are considered potential therapeutic tools to promote diabetic wound healing. The aim of this study was to investigate the effects of exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSC-Exos) on angiogenesis under high glucose (HG) conditions in vivo and in vitro and to explore the underlying mechanisms.Methods: HucMSC-Exos were used to treat diabetic wounds and human umbilical vascular endothelial cells (HUVECs) exposed to HG. Wound healing and angiogenesis were assessed in vivo. The biological characteristics of HUVECs were examined in vitro. Expression of pro-angiogenesis genes in HUVECs was also examined by western blotting. The miRNAs contained within hucMSC-Exos were identified using miRNA microarrays and qRT-PCR. The roles of selected miRNAs in angiogenesis were assessed using specific agomirs and inhibitors.Results: In vivo, local application of hucMSC-Exos enhanced wound healing and angiogenesis. In vitro, hucMSC-Exos reduced senescence of HG-treated HUVECs and promoted proliferation, migration, and tube formation by inhibiting phosphatase and tensin homolog (PTEN) expression and activating the AKT/HIF-1α/VEGF pathways. MiR-221-3p was enriched in hucMSC-Exos. In vitro, MiR-221-3p downregulated PTEN and activated the AKT/HIF-1α/VEGF pathway to promote proliferation, migration, and tube formation in HG-treated HUVECs. In vivo, miR-221-3p agomirs mimicked the effects of hucMSC-Exos on wound healing and angiogenesis, whereas miR-221-3p inhibitors reversed their effects.Conclusions: Our findings suggest that hucMSC-Exos have regenerative and protective effects on HG-induced senescence in endothelial cells via transfer of miR-221-3p, thereby accelerating diabetic wound healing. Thus, hucMSC-Exos may be promising therapeutic candidates for improving diabetic wound angiogenesis.

Principles of wound healing and growth factor considerations

1993 ◽  
Vol 83 (4) ◽  
pp. 223-227 ◽  
Author(s):  
SJ Skokan ◽  
RH Davis
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Wound Repair ◽  
Wound Closure ◽  
Cellular Proliferation ◽  
Positive Influence ◽  
Surgical Wounds ◽  
And Migration ◽  
Proliferation And Migration

This review examines some of the important principles in wound repair and significant considerations for the use of growth factors. Moisture provides a positive influence on the mechanical and hormonal aspects of wounds. Atraumatic closure of surgical wounds and postoperative care and the types of wound closure are discussed. Cellular proliferation and migration in wounds are central features regarding growth factors.

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