Healing of Full-Thickness Wounds Using Platelet-Rich Fibrin Seeded with Adipose Stem Cells in a Diabetic Mouse Model

2020 ◽  
Vol 10 (3) ◽  
pp. 315-322
Author(s):  
Yanping Guo ◽  
Jing Liu ◽  
Plastic Surgery Department, Nanjing Medical U ◽  
Qiang Li ◽  
Department of Ear Reconstruction, Plastic Sur ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Laser Scanning ◽  
Wound Repair ◽  
Subcutaneous Fat ◽  
Cell Activity ◽  
Therapeutic Effects ◽  
Diabetic Wound ◽  
Platelet Rich Fibrin ◽  
Diabetic Wounds

Diabetic wounds are refractory to spontaneous healing and treatment regimes due to their detrimental nature. Adipose derived stem cells (ASCs) hold great potential in stem cell-based therapies. However, insufficient cell activity and survival after transplantation dramatically reduce the therapeutic effects. Platelet-rich fibrin (PRF) is a great source of growth factors and has been widely used in clinical practice, but few studies explored its application in diabetic wounds. This study was designed to investigate therapeutic effect of PRF as a delivery scaffold of ASCs on promoting healing of diabetic wound in a mouse model. ASCs isolated from subcutaneous fat were cultured in the three-dimensional PRF scaffold for 3 and 7 days, respectively. H&E staining, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM) observation revealed that ASCs could survive and proliferate in PRF. Cell numbers in PRF increased dramatically in the duration of 7 days post-seeding. Meanwhile, it is revealed that conditioned medium of PRF enhanced ASCs proliferation and migration in an in vitro wound model. Furthermore, transplantation of PRF alone or PRF loaded with ASCs improved significantly diabetic wound repair, respectively. Capillary density in wounds received either PRF or PRF-ASCs was significantly higher than wounds without intervention. A in vivo survival assay was also conducted to find that PRF could maintain ASCs cells survive in diabetic wounds. Our study indicated that PRF, in particular that loaded with ASCs, can be considered as a promising approach in the treatment of diabetic wounds.

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 .

Graphene Oxide Accelerate Diabetic Wound Repair by Inhibiting Apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 Pathway

2021 ◽  
Author(s):  
Zhe Ji ◽  
Feifei Chen ◽  
Shuai Yang ◽  
Caiqi Shen ◽  
Hanxiao Wei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Repair ◽  
Target Gene ◽  
Diabetic Wound ◽  
Mirna Sponge ◽  
Downstream Signaling ◽  
Proliferation And Differentiation ◽  
Rna Immunoprecipitation ◽  
Auxiliary Material ◽  
Diabetic Wounds

Abstract BackgroundGraphene oxide (GO) has been proven in many studies to promote the proliferation and differentiation of a variety of stem cells, but its effect on the apoptosis of adipose-derived mesenchymal stem cells (Ad-MSCs) is still unclear. Apoptosis is one of the most important factors in the treatment of diabetic wounds by stem cells. Therefore, we explored its therapeutic effect on diabetic wounds by studying the effect of GO on the apoptosis of Ad-MSCs.MethodsqRT-PCR was used to detect the expression of lncRNAs, miRNAs and mRNAs in Ad-MSCs. RNA immunoprecipitation (RIP), RNA pull-down and luciferase assays were used to detect the interaction of the specific lncRNA, miRNA and mRNA. The effects of Linc00324 on Ad-MSCs cells apoptosis were explored by flow cytometer, TUNEL assay and Western blot. Diabetic wound was established to explore the function of Linc00324 on Ad-MSCs repairing ability in vivo.ResultsGO inhibited the apoptosis of Ad-MSCs caused by high glucose, and Linc00324 was one of the factors contributing to its effect. In terms of mechanism, RIP and RNA-Pull-down confirmed Linc00324 could directly interact with miR-7977, and then acted as a miRNA sponge to regulate the expression of miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. ConclusionsOverall, this study highlights that GO maybe a superior auxiliary material for Ad-MSCs to repair diabetic wounds via Linc00324/miR-7977/STK4 pathway.

scholarly journals Mesenchymal stem cells promote incision wound repair in a mouse model

2017 ◽  
Vol 16 (6) ◽  
pp. 1317 ◽  
Author(s):  
Dong-Jie Li ◽  
Chuan-An Shen ◽  
Tian-Jun Sun ◽  
Lin Zhang ◽  
Hu-Ping Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Wound Repair ◽  
Incision Wound

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 Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells on Concanavalin A-Induced Acute Liver Injury in Mice

Cell Medicine ◽  
2017 ◽  
Vol 9 (1-2) ◽  
pp. 21-33 ◽  
Author(s):  
Yasuma Yoshizumi ◽  
Hiroshi Yukawa ◽  
Ryoji Iwaki ◽  
Sanae Fujinaka ◽  
Ayano Kanou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Mouse Model ◽  
Cell Therapy ◽  
Concanavalin A ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Immunomodulatory Effects

Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS). The proliferation of LMCs was efficiently suppressed in a dose-dependent manner by ASCs in the cases of PMA plus ionomycin stimulation and ConA stimulation, but not in the case of LPS stimulation. The in vivo effects of transplanted ASCs were examined in the murine FHF model induced by ConA administration. The ALT levels and histological inflammatory changes in the ConA-administered mice were apparently relieved by the transplantation of ASCs. The analysis of mRNA expression patterns in the livers indicated that the expressions of the cytokines such as Il-6, Il-10, Ifn-γ, and Tnf-α, and the cell surface markers such as Cd3γ, Cd4, Cd8α, Cd11b, and Cd11c were downregulated in the ASC-transplanted mice. The immunomodulatory and therapeutic effects of ASCs were confirmed in the mouse model both in vitro and in vivo. These suggest that the cell therapy with ASCs is beneficial for the treatment of FHF.

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 Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis

Theranostics ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 1607-1623 ◽  
Author(s):  
Chun-Yuan Chen ◽  
Shan-Shan Rao ◽  
Lu Ren ◽  
Xiong-Ke Hu ◽  
Yi-Juan Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Urine ◽  
Wound Repair ◽  
Diabetic Wound

scholarly journals Novel Transplant of Combined Platelet-rich Fibrin Releasate and Bone Marrow Stem Cells Prevent Bone Loss in Ovariectomized Osteoporotic Mice

2020 ◽  
Author(s):  
chin chean wong ◽  
Jeng-Hao Liao ◽  
Shi-Yuan Sheu ◽  
Po-Yu Lin ◽  
Chih-Hwa Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Untreated Control ◽  
Single Injection ◽  
Bone Marrow Stem Cells ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Platelet Rich Fibrin ◽  
Injection Group ◽  
Bone Disorder

Abstract Background: Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture. Methods: In this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality. Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed. Results: Postmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control.Conclusion: The systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.

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