Involvements of γδT Lymphocytes in Acute and Chronic Skin Wound Repair

AbstractEffective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.

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THE OIL FROM MORINGA OLEIFERA SEEDS ACCELERATE CHRONIC SKIN WOUND HEALING

Phytomedicine Plus ◽

10.1016/j.phyplu.2021.100099 ◽

2021 ◽

pp. 100099

Author(s):

Ana Clara Sans Salomão Brunow Ventura ◽

Thalita de Paula ◽

Jenifer Pendiuk Gonçalves ◽

Bruna da Silva Soley ◽

Ananda Beatriz Munhoz Cretella ◽

...

Keyword(s):

Wound Healing ◽

Moringa Oleifera ◽

Skin Wound ◽

Skin Wound Healing ◽

Chronic Skin

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A Novel Xenograft Model Demonstrates Human Fibroblast Behavior During Skin Wound Repair and Fibrosis

Advances in Wound Care ◽

10.1089/wound.2020.1392 ◽

2021 ◽

Author(s):

Mimi Borrelli ◽

Abra H Shen ◽

Michelle Griffin ◽

Shamik Mascharak ◽

Sandeep Adem ◽

...

Keyword(s):

Human Fibroblast ◽

Wound Repair ◽

Xenograft Model ◽

Skin Wound

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Abstract 13373: Exercise Improves Angiogenic Function of Circulating Exosomes in Type 2 Diabetes: Role of Extracellular SOD

Circulation ◽

10.1161/circ.142.suppl_3.13373 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kareem Abdelsaid ◽

Sudhahar Varadarajan ◽

Archita Das ◽

Yutao Liu ◽

Xuexiu Fang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Wound Healing ◽

Endothelial Dysfunction ◽

Wound Repair ◽

Cell Communication ◽

Tube Formation ◽

Skin Wound ◽

Skin Wound Healing

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.

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Adipose-derived stromal/stem cells improve epidermal homeostasis

Scientific Reports ◽

10.1038/s41598-019-54797-5 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Mariko Moriyama ◽

Shunya Sahara ◽

Kaori Zaiki ◽

Ayumi Ueno ◽

Koichi Nakaoji ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Culture System ◽

Wound Repair ◽

Cell Types ◽

Skin Wound ◽

Epidermal Keratinocytes ◽

Stromal Stem Cells ◽

Collagen Vitrigel

AbstractWound healing is regulated by complex interactions between the keratinocytes and other cell types including fibroblasts. Recently, adipose-derived mesenchymal stromal/stem cells (ASCs) have been reported to influence wound healing positively via paracrine involvement. However, their roles in keratinocytes are still obscure. Therefore, investigation of the precise effects of ASCs on keratinocytes in an in vitro culture system is required. Our recent data indicate that the epidermal equivalents became thicker on a collagen vitrigel membrane co-cultured with human ASCs (hASCs). Co-culturing the human primary epidermal keratinocytes (HPEK) with hASCs on a collagen vitrigel membrane enhanced their abilities for cell proliferation and adhesion to the membrane but suppressed their differentiation suggesting that hASCs could maintain the undifferentiated status of HPEK. Contrarily, the effects of co-culture using polyethylene terephthalate or polycarbonate membranes for HPEK were completely opposite. These differences may depend on the protein permeability and/or structure of the membrane. Taken together, our data demonstrate that hASCs could be used as a substitute for fibroblasts in skin wound repair, aesthetic medicine, or tissue engineering. It is also important to note that a co-culture system using the collagen vitrigel membrane allows better understanding of the interactions between the keratinocytes and ASCs.

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A Fibrous Hybrid Patch Couples Cell-Derived Matrix and Poly(l-lactide-co-caprolactone) for Endothelial Cells Delivery and Skin Wound Repair

ACS Biomaterials Science & Engineering ◽

10.1021/acsbiomaterials.8b01118 ◽

2018 ◽

Vol 5 (2) ◽

pp. 900-910 ◽

Cited By ~ 6

Author(s):

Ping Du ◽

Cininta Casavitri ◽

Muhammad Suhaeri ◽

Peng-Yuan Wang ◽

Jong Ho Lee ◽

...

Keyword(s):

Endothelial Cells ◽

Wound Repair ◽

Skin Wound

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Systemic and topical administration of spermidine accelerates skin wound healing

10.21203/rs.3.rs-111107/v1 ◽

2020 ◽

Author(s):

Daisuke Ito ◽

Hiroyasu Ito ◽

Takayasu Ideta ◽

Ayumu Kanbe ◽

Soranobu Ninomiya ◽

...

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Wound Repair ◽

Healing Process ◽

Topical Administration ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

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In-depth Study of Alkaline Fibroblast Growth Factor to Promote Effective Mechanism of Skin Wound Repair

2018 3rd International Conference on Life Sciences, Medicine, and Health (ICLSMH 2018) ◽

10.25236/iclsmh.18.003 ◽

2018 ◽

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Wound Repair ◽

Skin Wound ◽

Fibroblast Growth ◽

Effective Mechanism ◽

Depth Study

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Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Burns & Trauma ◽

10.1093/burnst/tkaa028 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Pengcheng Xu ◽

Yaguang Wu ◽

Lina Zhou ◽

Zengjun Yang ◽

Xiaorong Zhang ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Wound Repair ◽

Chronic Wounds ◽

Platelet Rich Plasma ◽

Skin Wound ◽

Local Inflammation ◽

Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

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