scholarly journals Rigenera protocol: Elucidation of the mechanisms involved in wound healing

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Gabriele Ceccarelli ◽  
Martina Balli ◽  
Riccardo Bellazzi ◽  
Maurilio Sampaolesi ◽  
Gabriella Cusella
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Primary Fibroblast ◽  
Fibroblast Migration

In this study, we show an approach that follow 3R guidelines in order to demonstrate how Autologous Micrografts (AMG) modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation.

scholarly journals Effect of two homeopathic remedies at different degrees of dilutions on the wound closure of 3T3 fibroblasts in in vitro scratch assay

2021 ◽  
Vol 11 (40) ◽  
pp. 164-165
Author(s):  
Katarina Hostanska ◽  
Matthias Rostock ◽  
Stephan Baumgartner ◽  
Reinhard Saller
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Closure ◽  
Hypericum Perforatum ◽  
Calendula Officinalis ◽  
Arnica Montana ◽  
Fibroblast Migration ◽  
3T3 Fibroblasts ◽  
Nih 3T3

Background: Since ancient times, preparations from traditional medicinal plants e.g. Arnica montana, Calendula officinalis or Hypericum perforatum have been used for different wound healing purposes. The aim of this study was to investigate the efficacy of the commercial low dilution homeopathic remedy Similasan® Arnica plus Spray, a preparation of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712-2) and medium diluted SIM WuS (Petroleum 15x, Arnica montana 15x, Calcium fluoratum 12x, Calendula officinalis 12x, Hepar sulfuris 12x and Mercurius solubilis 15x; 1101-4), on the wound healing in cultured NIH 3T3 fibroblasts. Both remedies were from Similasan AG (Jonen, Switzerland) and prepared according the German Homoeopathic Pharmacopoeia (GHP) following descriptions 4a for arnica, 3a for marigold and St. John’s wort, 2a for comfrey, 5a for petroleum, and 6 for calcium fluoride, hepar sulfuris and mercurius solubilis. Materials and Methods: Cell proliferation, migration and wound closure promoting effect of the preparations (0712-2, 1101- 4) and their succussed solvents (0712-1, 1101-3) were investigated on mouse NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined wound area. All assays were performed in three independent controlled experiments. In some experiments diluted unsuccussed alcohol (0712-3) was also investigated. Results: Preparations (0712-1), (0712-2), (0712-3), (1101-3) and (1101-4) were investigated at decimal dilution steps from 1x to 4x. Cell viabilty was not affected by any of the substances and (0712-1) and (0712-2) showed no stimulating effect on cell proliferation. Preparation (0712-2) exerted a stimulating effect on fibroblast migration (31.7%) vs 15% with succussed solvent (0712-1) at 1:100 dilutions (p0.05). Positive control 2 ng/ml EGF increased migratory activity of cells by 49.8%. Preparation (0712-2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p

scholarly journals Fibroblast state switching orchestrates dermal maturation and wound healing

2017 ◽  
Author(s):  
Emanuel Rognoni ◽  
Angela Oliveira Pisco ◽  
Toru Hiratsuka ◽  
Kalle Sipilä ◽  
Julio M. Belmonte ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Therapeutic Strategies ◽  
Skin Regeneration ◽  
Negative Feedback Loop ◽  
Fibroblast Proliferation ◽  
Tissue Architecture ◽  
Fibroblast Migration

SummaryMurine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.Standfirst textWe show that fibroblast behaviour switching between two distinct states – proliferating and depositing ECM - is necessary and sufficient to define dermal architecture. Understanding this interdependence is critical for identifying new therapeutic strategies to enhance skin regeneration.HighlightsTissue-scale coordination in murine dermis is driven by the interdependence of cell proliferation and ECM depositionThe tissue architecture is set by a negative feedback loop between ECM deposition/remodelling and proliferationFibroblast lineages lose segregation with ageFibroblast migration is the critical discriminator between dermal development and wound healing

scholarly journals Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

2019 ◽  
Author(s):  
Martina Balli ◽  
Francesca Vitali ◽  
Adrian Janiszewski ◽  
Ellen Caluwé ◽  
Alvaro Cortés-Calabuig ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Skin Lesions ◽  
Wound Healing Process ◽  
Primary Fibroblast ◽  
Fibroblast Migration ◽  
Healing Response ◽  
Wound Healing Response

AbstractDefective fibroblast migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for a faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of extracellular signal-regulated kinase (ERK) pathway and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process.

scholarly journals Anti-inflammatory, wound healing and antioxidant potential of compounds from Dioscorea bulbifera L. bulbils

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243632
Author(s):  
Prapaporn Chaniad ◽  
Supinya Tewtrakul ◽  
Teeratad Sudsai ◽  
Supat Langyanai ◽  
Kantarakorn Kaewdana
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Radical Scavenging ◽  
Dermal Fibroblasts ◽  
No Production ◽  
Fibroblast Migration ◽  
Raw264.7 Macrophages ◽  
Crude Extracts ◽  
Dioscorea Bulbifera ◽  
Anti Inflammatory

Background Dioscorea bulbifera L. (Dioscoreaceae) has been traditionally used in Thai folk medicine as a diuretic and anthelmintic, for longevity preparations, and for wound and inflammation treatment. This plant is also commonly used in traditional Indian and Chinese medicines in the treatment of sore throat, gastric cancer, rectal carcinoma and goiters. However, the wound healing effects of the active compounds in this plant have not been investigated. Objective This study aimed to identify compounds responsible for the wound healing activity of D. bulbifera and determine their potential anti-inflammatory and antioxidant activities. Methods Crude extracts of D. bulbifera bulbils, their derived fractions and eleven purified compounds were tested for anti-inflammatory activity against LPS-induced NO production in RAW264.7 macrophages. The wound healing effects were evaluated via cell proliferation and migration assays using human dermal fibroblasts (HDFs), and the antioxidant effects were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (•OH) scavenging activity assays. Results 15,16-Epoxy-6α-O-acetyl-8β-hydroxy-19-nor-clero-13(16),14-diene-17,12;18,2-diolide (2), (+)-catechin (5), quercetin (6) and myricetin (11) exhibited significantly potent wound healing effects and promoted marked cell proliferation, resulting in % viabilities of 107.4–137.6, 121.1–151.9, 98.0–131.9, 90.9–115.9, respectively. Among them, (+)-catechin produced the highest % cell migration, resulting in 100.0% wound closure sooner (at day 2) than the other compounds. In addition, 1 μg/ml (+)-catechin significantly increased fibroblast migration by 2.4-fold compared to that in the control after 24 h. Regarding anti-inflammatory properties, kaempferol (7) and quercetin (6) decreased (p < 0.005) NO production, with IC50 values of 46.6 and 56.2 μM, respectively. In addition, the crude extracts, solvent fractions and flavonoid compounds were also found to possess marked antioxidant activity in both DPPH and •OH radical scavenging assays. Conclusions These findings provide more evidence to support the traditional use of D. bulbifera for the treatment of wounds and inflammation.

scholarly journals IL-1β Impaired Diabetic Wound Healing by Regulating MMP-2 and MMP-9 through the p38 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jiezhi Dai ◽  
Junjie Shen ◽  
Yimin Chai ◽  
Hua Chen
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Human Fibroblasts ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Fibroblast Migration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Diabetes mellitus is one of the most prominent metabolic disorders in the world, and insulin resistance in diabetic patients leads to several complications including increased inflammation and delayed wound healing. Fibroblast migration and reepithelialization play a significant role in wound healing. In this study, we explored the effects of IL-1β signaling on proliferation and migration of human fibroblasts from diabetic wound tissues. We observed elevated levels of IL-1β in samples from diabetic patients when compared to normal wound tissues. At high concentrations, IL-1β inhibited cell proliferation and migration in ex vivo fibroblast cultures. Moreover, expression of matrix metalloproteinases (MMPs) was upregulated, and tissue inhibitor of metalloproteinases (TIMPs) was downregulated in diabetic wound tissues and cells. These effects were regulated by levels of IL-1β. Furthermore, IL-1β induced p38 phosphorylation thereby activating the p38 MAPK pathway that in turn regulated the expression of MMPs and TIMPs. Together, our study identifies a novel mechanism behind delayed wound closure in diabetes mellitus that involves IL-1β-dependent regulation of cell proliferation and migration.

Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sushmitha Sriramulu ◽  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Human Keratinocytes ◽  
Human Umbilical Cord ◽  
Hacat Cells ◽  
And Migration

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

In vitro and in vivo Effect of Platelet-Rich Plasma-Based Autologous Topical Serum on Cutaneous Wound Healing

2021 ◽  
pp. 1-13
Author(s):  
Eduardo Anitua ◽  
Victoria Muñoz ◽  
Libe Aspe ◽  
Roberto Tierno ◽  
Adrian García-Salvador ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Damage ◽  
Collagen Synthesis ◽  
Dermal Fibroblast ◽  
Platelet Rich Plasma ◽  
Cell Activity ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Fibroblast Migration ◽  
Edge Contraction

<b><i>Introduction:</i></b> Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions. <b><i>Objective:</i></b> The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care. <b><i>Methods:</i></b> Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed. <b><i>Results:</i></b> ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events. <b><i>Conclusion:</i></b> This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.

scholarly journals The cell biology of regeneration

2012 ◽  
Vol 196 (5) ◽  
pp. 553-562 ◽  
Author(s):  
Ryan S. King ◽  
Phillip A. Newmark
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Biology ◽  
Progenitor Cell ◽  
Complex Structures ◽  
Regenerative Processes ◽  
Cellular Behavior ◽  
Positional Identity ◽  
Progenitor Cell Proliferation ◽  
Functional Analyses

Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration.

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