scholarly journals Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis

2017 ◽  
Vol 49 (10) ◽  
pp. 541-548 ◽  
Author(s):  
Junwang Xu ◽  
Carlos Zgheib ◽  
Maggie M. Hodges ◽  
Robert C. Caskey ◽  
Junyi Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Protein Content ◽  
Collagen I ◽  
Extracellular Matrix Protein ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.

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.

Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

2021 ◽  
Vol 22 ◽  
Author(s):  
Jiang-wen Wang ◽  
Yuan-zheng Zhu ◽  
Xuan Hu ◽  
Jia-ying Nie ◽  
Zhao-hui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mouse Model ◽  
Adipose Derived Stem Cells ◽  
Collagen Deposition ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors

2019 ◽  
Vol 312 (5) ◽  
pp. 325-336 ◽  
Author(s):  
Mona Saheli ◽  
Mohammad Bayat ◽  
Rasoul Ganji ◽  
Farzane Hendudari ◽  
Raziyeh Kheirjou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Human Mesenchymal Stem Cells ◽  
Diabetic Wound ◽  
Diabetic Wound Healing

scholarly journals Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chandrama Shrestha ◽  
Liling Zhao ◽  
Ke Chen ◽  
Honghui He ◽  
Zhaohui Mo
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Umbilical Cord ◽  
Subcutaneous Administration ◽  
Conditioned Media ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Significant Difference ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds.Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n=6;P<0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-βand KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds.Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

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

2019 ◽  
Vol 8 (4) ◽  
pp. 404-414 ◽  
Author(s):  
Agnes Dwi Ariyanti ◽  
Jianqi Zhang ◽  
Olivia Marcelina ◽  
Dyah Ari Nugrahaningrum ◽  
Guixue Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Diabetic Wound ◽  
Diabetic Wound Healing
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