Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial

2021 ◽  
Author(s):  
Joris A van Dongen ◽  
Joeri v Boxtel ◽  
Mustafa Uguten ◽  
Linda A Brouwer ◽  
Karin M Vermeulen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Histological Analysis ◽  
Stromal Vascular Fraction ◽  
Scar Formation ◽  
Patient Questionnaire ◽  
Matrix Remodeling ◽  
Double Blind ◽  
Tissue Samples ◽  
Scar Assessment ◽  
The Impact

Abstract Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. Tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. Objectives In this study, we hypothesized that tSVF reduces post-surgical scar formation. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of one breast and a placebo injection in the contralateral breast to serve as an intra-patient control. Primary outcome was scar quality using the patient and observer scar assessment scale (POSAS). Secondary outcomes were obtained with photograph evaluation and histological analysis of scar tissue samples. Results Thirty-four of 40 patients completed follow-up. Six months postoperatively, injection of tSVF had significantly improved postoperative scar appearance as assessed by POSAS questionnaire (observer and patient questionnaire). No difference was observed at 12 months postoperatively. No improvement was seen based on the evaluation of photographs and histological analysis of postoperative scars between both groups. Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperative, without any noticeable advantageous effects seen at 12 months.

scholarly journals Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hongsen Bi ◽  
Hui Li ◽  
Chen Zhang ◽  
Yiqing Mao ◽  
Fangfei Nie ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Healing Process ◽  
Stromal Vascular Fraction ◽  
Wound Healing Process ◽  
Matrix Remodeling ◽  
Skin Defect ◽  
The Impact

Abstract Background A refractory wound is a typical complication of diabetes and is a common outcome after surgery. Current approaches have difficulty in improving wound healing. Recently, non-expanded stromal vascular fraction (SVF), which is derived from mature fat, has opened up new directions for the treatment of refractory wound healing. The aim of the current study is to systematically investigate the impact of SVF on wound healing, including the rate and characteristics of wound healing, ability of fibroblasts to migrate, and blood transport reconstruction, with a special emphasis on their precise molecular mechanisms. Methods SVF was isolated by digestion, followed by filtration and centrifugation, and then validated by immunocytochemistry, a MTS proliferation assay and multilineage potential analysis. A wound model was generated by creating 6-mm-diameter wounds, which include a full skin defect, on the backs of streptozocin-induced hyperglycemic mice. SVF or human adipose-derived stem cell (hADSC) suspensions were subcutaneously injected, and the wounds were characterized over a 9-day period by photography and measurements. A scratch test was used to determine whether changes in the migratory ability of fibroblasts occurred after co-culture with hADSCs. Angiogenesis was observed with human umbilical vein endothelial cells. mRNA from fibroblasts, endotheliocyte, and skin tissue were sequenced by high-throughput RNAseq, and differentially expressed genes, and pathways, potentially regulated by SVF or hADSCs were bioinformatically analyzed. Results Our data show that hADSCs have multiple characteristics of MSC. SVF and hADSCs significantly improved wound healing in hyperglycemic mice. hADSCs improve the migratory ability of fibroblasts and capillary structure formation in HUVECs. SVF promotes wound healing by focusing on angiogenesis and matrix remodeling. Conclusions Both SVF and hADSCs improve the function of fibroblast and endothelial cells, regulate gene expression, and promote skin healing. Various mechanisms likely are involved, including migration of fibroblasts, tubulogenesis of endothelial cells through regulation of cell adhesion, and cytokine pathways.

Understanding the mechanisms that determine extracellular matrix remodeling in the infarcted myocardium

2019 ◽  
Vol 47 (6) ◽  
pp. 1679-1687
Author(s):  
Mavis A.A. Tenkorang ◽  
Upendra Chalise ◽  
Michael J. Daseke, II ◽  
Shelby R. Konfrst ◽  
Merry L. Lindsey
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Inflammatory Response ◽  
Current Knowledge ◽  
Scar Formation ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Infarcted Myocardium

Myocardial Infarction (MI) initiates a series of wound healing events that begins with up-regulation of an inflammatory response and culminates in scar formation. The extracellular matrix (ECM) is intricately involved in all stages from initial break down of existing ECM to synthesis of new ECM to form the scar. This review will summarize our current knowledge on the processes involved in ECM remodeling after MI and identify the gaps that still need to be filled.

Impact of wound duration on diabetic foot ulcer healing: evaluation of a new sucrose octasulfate wound dressing

2020 ◽  
Vol 29 (10) ◽  
pp. 543-551
Author(s):  
Ralf Lobmann ◽  
Arthur Grünerbel ◽  
Holger Lawall ◽  
Claas Lüdemann ◽  
Stephan Morbach ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cost Effectiveness ◽  
Markov Model ◽  
Diabetic Foot ◽  
Treatment Costs ◽  
Wound Dressings ◽  
Double Blind ◽  
Direct Treatment ◽  
Sucrose Octasulfate ◽  
The Impact

Objective: A common and frequent complication of diabetes is diabetic foot ulcers (DFU), which can have high treatment costs and severe adverse events. This study aims to evaluate the effects of wound duration on wound healing and the impact on costs, including treatment with a new sucrose octasulfate dressing compared with a control dressing. Method: Based on the Explorer study (a two-armed randomised double-blind clinical trial), a cost-effectiveness analysis compared four different patient groups distinguished by their wound duration and additionally two DFU treatment options: a sucrose octasulfate dressing and a neutral dressing (as control). Clinical outcomes and total direct costs of wound dressings were evaluated over 20 weeks from the perspective of the Social Health Insurance in Germany. Simulation of long-term outcomes and costs were demonstrated by a five cycle Markov model. Results: The results show total wound healing rates between 71% and 14.8%, and direct treatment costs for DFU in the range of €2482–3278 (sucrose octasulfate dressing) and €2768–3194 (control dressing). Patients with a wound duration of ≤2 months revealed the highest wound healing rates for both the sucrose octasulfate dressing and control dressing (71% and 41%, respectively) and had the lowest direct treatment costs of €2482 and €2768, respectively. The 100-week Markov model amplified the results. Patients with ≤2 months' wound duration achieved wound healing rates of 98% and 88%, respectively and costs of €3450 and €6054, respectively (CE=€3520, €6864). Sensitivity analysis revealed that the dressing changes per week were the most significant uncertainty factor. Conclusion: Based on the findings of this study, early treatment of DFU with a sucrose octasulfate dressing is recommended from a health economic view due to lower treatment costs, greater cost-effectiveness and higher wound healing rates.

scholarly journals SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial

2019 ◽  
Vol 24 (3) ◽  
pp. 200-207 ◽  
Author(s):  
Mehdi H Shishehbor ◽  
John Rundback ◽  
Matthew Bunte ◽  
Tarek A Hammad ◽  
Leslie Miller ◽  
...  
Keyword(s):  
Wound Healing ◽  
Limb Ischemia ◽  
Viral Gene ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
End Point ◽  
Angiographic Demonstration ◽  
Healing Score ◽  
The Impact

The efficacy of biologic therapies in critical limb ischemia (CLI) remains elusive, in part, due to limitations in trial design and patient selection. Using a novel design, we examined the impact of complementing revascularization therapy with intramuscular JVS-100 – a non-viral gene therapy that activates endogenous regenerative repair pathways. In this double-blind, placebo-controlled, Phase 2B trial, we randomized 109 patients with CLI (Rutherford class V or VI) to 8 mg or 16 mg intramuscular injections of placebo versus JVS-100. Patients were eligible if they persistently had reduced forefoot perfusion, by toe–brachial index (TBI) or skin perfusion pressure (SPP), following successful revascularization with angiographic demonstration of tibial arterial flow to the ankle. The primary efficacy end point was a 3-month wound healing score assessed by an independent wound core laboratory. The primary safety end point was major adverse limb events (MALE). Patients’ mean age was 71 years, 33% were women, 79% had diabetes, and 8% had end-stage renal disease. TBI after revascularization was 0.26, 0.27, and 0.26 among the three groups (placebo, 8 mg, and 16 mg injections, respectively). Only 26% of wounds completely healed at 3 months, without any differences between the three groups (26.5%, 26.5%, and 25%, respectively). Similarly, there were no significant changes in TBI at 3 months. Three (2.8%) patients died and two (1.8%) had major amputations. Rates of MALE at 3 months were 8.8%, 20%, and 8.3%, respectively. While safe, JVS-100 failed to improve wound healing or hemodynamic measures at 3 months. Only one-quarter of CLI wounds healed at 3 months despite successful revascularization, highlighting the need for additional research in therapies that can improve microcirculation in these patients. ClinicalTrials.gov Identifier: NCT02544204

scholarly journals SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 160
Author(s):  
Ashang L. Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Collagen Scaffold ◽  
Diabetic Patients ◽  
Matrix Remodeling ◽  
Adipose Derived Stem Cells ◽  
Cell Therapies ◽  
Gene And Protein Expression ◽  
The Impact

Non-healing diabetic foot ulcers (DFUs) can lead to leg amputation in diabetic patients. Autologous stem cell therapy holds some potential to solve this problem; however, diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen–chondroitin sulfate (coll–CS) scaffold, functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold), can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). We assessed the impact of the gene-activated scaffold on diabetic ADSCs by comparing their response against healthy ADSCs cultured on a gene-free scaffold over two weeks. Overall, we found that the gene-activated scaffold could restore the pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream β-arrestin signaling, as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also exhibited pro-wound healing features characterized by active matrix remodeling of the provisional fibronectin matrix and basement membrane protein collagen IV. The gene-activated scaffold also induced a controlled pro-healing response in the healthy ADSCs by disabling early developmental factors signaling while promoting the expression of tissue remodeling components. Conclusively, we show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs, paving the way for autologous stem cell therapies combined with novel biomaterials to treat DFUs.

Insight on Ameliorative Role of Selenium Nanoparticles and Niacin in Wound Healing on Adult Female Albino Mice

2020 ◽  
Vol 14 (3) ◽  
pp. 169-186
Author(s):  
Marwa Emam ◽  
Akaber T. Keshta ◽  
Yasser M.A. Mohamed ◽  
Yasser A. Attia
Keyword(s):  
Wound Healing ◽  
Adult Female ◽  
Vascular Endothelial Cell ◽  
Skin Layer ◽  
Positive Control ◽  
Healing Time ◽  
Selenium Nanoparticles ◽  
Tissue Samples ◽  
Liver And Kidney ◽  
Albino Mice

Background: Wound healing is a complex process necessary for repairing damaged tissues and preventing infection. Selenium nanoparticles (Se NPs) were known due to their antioxidant and antimicrobial effects, also niacin has angiogenesis and antioxidant effects that are important in wound healing. Objective: The present study was conducted to investigate the effect of Se NPs and niacin in reducing and accelerating the wound healing time in mice. Methods: A simple wet chemical method has been modified to synthesize Se NPs in order to investigate their effect and niacin on reducing the wound healing in 80 adult female albino mice (250 mm2 full thickness open excision wound) that were divided into eight groups (10 mice/each). After 30-days, the mice were sacrificed, blood and tissue samples were taken for analysis. Results: The results showed that the percentage of wound area had been significantly reduced in Se NPs and niacin treated groups compared to the positive control. The level of Vascular Endothelial cell Growth Factor and Collagenase I in Se NPs and niacin groups significantly exceed those of other groups while Nitric Oxide (NO) was significantly decreased in treated groups. Liver and kidney functions showed the lower toxicity effect of Se NPs and niacin. Skin tissue showed the wound healing effect of Se NPs and niacin by regenerating skin layer compared to the positive group. Conclusion: Se NPs and niacin play an important role in accelerating and reducing the time of wound healing while they were antagonistic to each other.

scholarly journals Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Lipid Mediator ◽  
Olive Pomace ◽  
Double Blind ◽  
Promising Alternative ◽  
Catabolic Enzymes ◽  
Platelet Activating Factor Acetylhydrolase ◽  
The Impact ◽  
By Products ◽  
Apparently Healthy

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

scholarly journals Activation of NF-κB signaling via cytosolic mitochondrial RNA sensing in kerotocytes with mitochondrial DNA common deletion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Zhou ◽  
Ludvig J. Backman ◽  
Patrik Danielson
Keyword(s):  
Wound Healing ◽  
Mitochondrial Dna ◽  
Scar Formation ◽  
Mitochondrial Rna ◽  
Peripheral Part ◽  
Double Stranded Rna ◽  
Corneal Wound ◽  
Biochemical Approach ◽  
Common Deletion ◽  
Underlying Mechanisms

AbstractScar formation as a result of corneal wound healing is a leading cause of blindness. It is a challenge to understand why scar formation is more likely to occur in the central part of the cornea as compared to the peripheral part. The purpose of this study was to unravel the underlying mechanisms. We applied RNA-seq to uncover the differences of expression profile in keratocytes in the central/peripheral part of the cornea. The relative quantity of mitochondrial RNA was measured by multiplex qPCR. The characterization of mitochondrial RNA in the cytoplasm was confirmed by immunofluoresence microscope and biochemical approach. Gene expression was analyzed by western blot and RT qPCR. We demonstrate that the occurrence of mitochondrial DNA common deletion is greater in keratocytes from the central cornea as compared to those of the peripheral part. The keratocytes with CD have elevated oxidative stress levels, which leads to the leakage of mitochondrial double-stranded RNA into the cytoplasm. The cytoplasmic mitochondrial double-stranded RNA is sensed by MDA5, which induces NF-κB activation. The NF-κB activation thereafter induces fibrosis-like extracellular matrix expressions and IL-8 mRNA transcription. These results provide a novel explanation of the different clinical outcome in different regions of the cornea during wound healing.

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