Advances in skin grafting and treatment of cutaneous wounds

Sun, Bryan K.; Siprashvili, Zurab; Khavari, Paul A.

doi:10.1126/science.1253836

Cited by 716 publications

(527 citation statements)

References 55 publications

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“…CXCL-8 may also promote homing of vascular endothelial cells to the skin ulcer area to increase angiogenesis, reduce hypoxia and accelerate ulcer healing. The healing of skin wounds involves the secretion of numerous cytokines and interactions between fibroblasts, vascular endothelial cells and various other cell types (39). As the present study evaluated the effect of CXCL-8 on only vascular endothelial cells, studies into the effects of CXCL-8 on other cell types are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…It has been observed that hypoxia stimulates HeLa cells to express high levels of CXCL-8, which subsequently promotes vascular endothelial cell homing and accelerates angiogenesis, leading to a reverse in the hypoxic environment of the tumor tissue, increased tumor cell proliferation and inhibition of cell apoptosis (38). During the process of skin wound healing, macrophages secrete high levels of CXCL-8, which then stimulates the recruitment of fibroblasts, vascular endothelial cells, hair follicle stem cells and others to the skin defect area through binding to CXCR1/2 (39)(40)(41). CXCL-8 also promotes vascular endothelial cell adhesion, accelerates angiogenesis, increases the deposition of extracellular matrix and promotes wound healing, which further indicates the importance of CXCL-8 in wound healing (39,40).…”

Section: Discussionmentioning

confidence: 99%

“…During the process of skin wound healing, macrophages secrete high levels of CXCL-8, which then stimulates the recruitment of fibroblasts, vascular endothelial cells, hair follicle stem cells and others to the skin defect area through binding to CXCR1/2 (39)(40)(41). CXCL-8 also promotes vascular endothelial cell adhesion, accelerates angiogenesis, increases the deposition of extracellular matrix and promotes wound healing, which further indicates the importance of CXCL-8 in wound healing (39,40). Thus, the use of CXCL-8 in cell-based treatments for hypoxic diseases may protect the transplanted cells, promote host cell homing and aid the repair of tissue damage.…”

Section: Discussionmentioning

confidence: 99%

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C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

Shen

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. C-X-C motif chemokine ligand 8 (CXCL-8) promotes cell homing and angiogenesis. However, under hypoxic conditions, the role of CXCL-8 in the homing of human umbilical vein endothelial cells (HUVECs), and its effect on the healing of skin ulcers caused by ischemia and hypoxia remain unknown. In the current study, assays measuring cell proliferation, in vitro angiogenesis and cell migration were performed to evaluate alterations in the proliferation, angiogenic capacity and chemotaxis of HUVECs treated with CXCL-8 protein and/or an Akt inhibitor (AZD5363 group) under hypoxic conditions. Changes in the levels of Akt, signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), malondialdehyde (MDA) and total-superoxide dismutase (total-SOD) were also detected by western blotting and ELISA. In addition, in vivo experiments were performed using a skin ulcer model in mice. Ischemic and hypoxic skin ulcers were created on the thighs of C57BL/6J mice, and the effects of CXCL-8 and HUVEC transplantation on the healing capacity of skin ulcers was determined by injecting mice with HUVECs and/or CXCL-8 recombinant protein (CXCL-8, HUVEC and HUVEC + CXCL-8 groups). Vascular endothelial cell homing, changes in vascular density and the expression of VEGF, SOD, EGF and MDA within the ulcer tissue were subsequently measured. In vitro experiments demonstrated that HUVEC proliferation, migration and tube forming capacity were significantly increased by CXCL-8 under hypoxic conditions. Additionally, levels of VEGF, MDA and SOD were significantly higher in the CXCL-8 group, though were significantly decreased by the Akt and STAT3 inhibitors. In vivo experiments demonstrated that the expression of VEGF, total-SOD and EGF proteins were higher in the skin ulcer tissue of mice treated with CXCL-8 + HUVEC, relative to mice treated with HUVECs alone. Furthermore, vascular endothelial cell homing and vascular density were significantly increased in the CXCL-8 + HUVEC group, indicating that combined use of HUVECs and CXCL-8 may promote the healing of ischemic skin ulcers. The present results demonstrate that CXCL-8 may stimulate vascular endothelial cells to secrete VEGF, SOD and other cytokines via the Akt-STAT3 pathway, which in turn serves a key regulatory role in the recruitment of vascular endothelial cells, reduction of hypoxia-related injury and promotion of tissue repair following hypoxic/ischemic injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

Shen

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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“…Investigations of recent years have shown that usage of iPSCs makes it possible to obtain effective tissue-engineered products for regenerative medicine including treatment skin wounds [39]. A good illustration is the work of Itoch et al [40] in which they elaborated a protocol of IPSCs differentiation into keratinocytes and dermal fibroblasts to be used in the treatment of recessive dystrophic epidermolysis bullosa.…”

Section: A Cellular Componentmentioning

confidence: 99%

Skin Tissue-Engineering Constructs and Stem Cells Application for the Skin Equivalents Creation (Review)

Meleshina¹,

Bystrova²,

Rogovaya³

et al. 2017

Sovrem Tehnol Med

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Development and introduction of new biotechnological analogues (equivalents) of tissues and organs into clinical practice, such as human skin equivalents (SE), designed for temporal or permanent replacement of damaged or destroyed tissue, remains an urgent problem of regenerative medicine. Currently, full-thickness SE as well as separate skin layers, which include living cells of different types, are being created and investigated. Since the ideal skin substitutes have not been created, the efforts of researchers in many countries are aimed at solving this problem.In our review, we present a comparative analysis of existing SE, both commercial and those being at the stage of preclinical study, analyze their structure and feasibility of application for solving experimental and clinical tasks. Characteristics of the three main variants of SE have also been considered. Examples of stem cell application for creation of skin equivalents have been given. The main advantages of using stem cells as a cell component of skin equivalents have been described.

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“…[2][3][4] Numerous growth factors, such as epidermal growth factor (EGF), transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), were considered the key regulators of the wound healing process. [5][6][7] It has been established that impaired chronic wound healing is associated with decreased secretion of endogenous growth factors. Therefore, provision of exogenous growth factors at precisely timed intervals would provide stimulation to induce faster reepithelialization, as well as reduce the risk of infection.…”

Section: Introductionmentioning

confidence: 99%

EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

et al. 2016

IJN

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Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair.

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Advances in skin grafting and treatment of cutaneous wounds

Cited by 716 publications

References 55 publications

C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

Skin Tissue-Engineering Constructs and Stem Cells Application for the Skin Equivalents Creation (Review)

EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

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