928 Combination bioengineered wound scaffolds containing timolol-preconditioned mesenchymal stem cells promote wound healing in diabetic mice

More and more evidence advises that circular RNAs (circRNAs) function critically in regulating different disease microenvironments. Our previous study found that autotransplantation of adipose-derived mesenchymal stem cells (ADSCs) promotes diabetes wound healing. Exosomes derived in ADSCs play an important regulatory role. This study aimed to characterize if mmu_circ_0000250 played a role in ADSC-exosome-mediated full-thickness skin wound repair in diabetic rats. Endothelial progenitor cells (EPCs) were selected to study the therapeutic mechanism of exosomes in high-glucose (HG)-induced cell damage and dysfunction. Analysis and luciferase reporter assay were utilized to explore the interaction among mmu_circ_0000250, miRNA (miR)-128-3p, and sirtuin (SIRT)1. The diabetic rats were used to confirm the therapeutic effect of mmu_circ_0000250 against exosome-mediated wound healing. Exosomes containing a high concentration of mmu_circ_0000250 had a greater therapeutic effect on restoration of the function of EPCs by promotion autophagy activation under HG conditions. Expression of mmu_circ_0000250 promoted SIRT1 expression by miR-128-3p adsorption, which was confirmed via luciferase reporter assay and bioinformatics analysis. In vivo, exosomes containing a high concentration of mmu_circ_0000250 had a more therapeutic effect on wound healing when compared with wild-type exosomes from ADSCs. Immunohistochemistry and immunofluorescence detection showed that mmu_circ_0000250 increased angiopoiesis with exosome treatment in wound skin and suppressed apoptosis by autophagy activation. In conclusion, we verified that mmu_circ_0000250 enhanced the therapeutic effect of ADSC-exosomes to promote wound healing in diabetes by absorption of miR-128-3p and upregulation of SIRT1. Therefore, these findings advocate targeting the mmu_circ_0000250/miR-128-3p/SIRT1 axis as a candidate therapeutic option for diabetic ulcers.

Download Full-text

Mesenchymal stem cells modified with angiopoietin-1 gene promote wound healing

Stem Cell Research & Therapy ◽

10.1186/scrt324 ◽

2013 ◽

Vol 4 (5) ◽

pp. 113 ◽

Cited By ~ 27

Author(s):

Yunling Li ◽

Lei Zheng ◽

Xia Xu ◽

Lili Song ◽

Yin Li ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Promote Wound Healing ◽

Angiopoietin 1

Download Full-text

Wharton’s jelly mesenchymal stem cells promote wound healing and tissue regeneration

Stem Cell Research & Therapy ◽

10.1186/scrt451 ◽

2014 ◽

Vol 5 (3) ◽

pp. 62 ◽

Cited By ~ 15

Author(s):

Lars-Peter Kamolz ◽

Maike Keck ◽

Cornelia Kasper

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Wharton’S Jelly ◽

Promote Wound Healing ◽

Wharton's Jelly

Download Full-text

Mesenchymal Stem Cells Coated by the Extracellular Matrix Promote Wound Healing in Diabetic Rats

Stem Cells International ◽

10.1155/2019/9564869 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Linhao Wang ◽

Fang Wang ◽

Liling Zhao ◽

Wenjun Yang ◽

Xinxing Wan ◽

...

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Diabetic Rats ◽

Skin Thickness ◽

Wound Area ◽

Promote Wound Healing ◽

Diabetes Model ◽

Diabetic Wound Healing

Objective. To investigate the effects of mesenchymal stem cells (MSCs) coated by the extracellular matrix (ECM) on wound healing in diabetic rats. Methods. Mesenchymal stem cells were cocultured with ECM. Cell viabilities were evaluated using MTT assay. The diabetes model was established using both STZ and high-glucose/fat methods in SD rats. A wound area was made on the middle of the rats’ back. MSCs or ECM-MSCs were used to treat the rats. HE staining and CD31 immunohistochemistry were used to detect the skin thickness and angiogenesis. Western blotting and qRT-PCR were conducted to determine the level of VEGF-α, PDGF, and EGF. Results. It was observed that treatment of ECM had no significant effects on the cell viability of ECM-MSCs. Wound area assay showed that both MSCs and ECM-MSCs could enhance the wound healing of diabetic rats and ECM-MSCs could further promote the effects. Both MSCs and ECM-MSCs could enhance angiogenesis and epithelialization of the wounds, as well as the expression of VEGF-α, PDGF, and EGF in wound tissues, while ECM-MSC treatment showed more obvious effects. Conclusion. Mesenchymal stem cells coated by the extracellular matrix could promote wound healing in diabetic rats. Our study may offer a novel therapeutic method for impaired diabetic wound healing.

Download Full-text

Neurotrophin-3 Accelerates Wound Healing in Diabetic Mice by Promoting a Paracrine Response in Mesenchymal Stem Cells

Cell Transplantation ◽

10.3727/096368912x657495 ◽

2013 ◽

Vol 22 (6) ◽

pp. 1011-1021 ◽

Cited By ~ 39

Author(s):

Lei Shen ◽

Wen Zeng ◽

Yang-Xiao Wu ◽

Chun-Li Hou ◽

Wen Chen ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Diabetic Mice ◽

Neurotrophin 3

Download Full-text

Vasculoprotective Effects of Combined Endothelial Progenitor Cells and Mesenchymal Stem Cells in Diabetic Wound Care: Their Potential Role in Decreasing Wound-Oxidative Stress

BioMed Research International ◽

10.1155/2013/459196 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Supakanda Sukpat ◽

Nipan Isarasena ◽

Jutamas Wongphoom ◽

Suthiluk Patumraj

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Wound Care ◽

Control Group ◽

Diabetic Mice ◽

Mice Model ◽

Endothelial Progenitor

To investigate whether the combined endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) could enhance angiogenesis and wound healing in diabetic mice. Balb/c nude mice were divided into five groups, including a control group, diabetic group (DM), DM injected with 1 × 106 cells MSCs, DM injected with 1 × 106 cells EPCs, and DM injected with combined 0.5 × 106 cells MSCs and 0.5 × 106 cells EPCs. After seven weeks, the mice were anesthetized, and bilateral full-thickness excision skin wounds were made on the dorsorostral back. The percentage of wound closure in DM group decreased significantly than in control and all other treated groups on day 7 and day 14 (P<0.005). On day 14, the percentage of capillary vascularity in combine-treated group was significantly higher than in DM (P<0.005). In the present study, we have demonstrated that the combined EPCs and MSCs can increase vascular endothelial growth factor (VEGF) level and angiogenesis which resulted in reduced neutrophil infiltration, decreased malondialdehyde (MDA) levels, and enhanced wound healing in diabetic mice model.

Download Full-text