Chemokine Regulation of Angiogenesis During Wound Healing

Bodnar, Richard J.

doi:10.1089/wound.2014.0594

Cited by 152 publications

(122 citation statements)

References 48 publications

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“…Angiogenesis, as a hallmark of wound healing, is regulated by complex control systems including proangiogenic and antiangiogenic factors and tightly controlled physiological balance between stimulatory and inhibitory signals related to new blood vessel formation . VEGF, being one of the most important proangiogenic factors, is a highly specific mitogen for endothelial cells .…”

Section: Discussionmentioning

confidence: 51%

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

Batičić

Pugel

Detel

et al. 2017

Wound Repair Regeneration

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Dipeptidyl peptidase IV (DPP IV/CD26) is a widely distributed multifunctional protein that plays a significant role in different physiological as well as pathological processes having a broad spectrum of bioactive substrates and immunomodulative properties. It has potential influence on different processes crucial for wound healing, including cell adhesion, migration, apoptosis, and extracellular matrix degradation. However, despite its known enzymatic and immunomodulative functions, limited data characterize the role of DPP IV/CD26 in cutaneous wound healing mechanisms. The aim of this study was to investigate the process of wound healing in conditions of CD26 deficiency in order to obtain better insights on the role of DPP IV/CD26 in cutaneous regeneration. Experimental wounds were made on the dorsal part of CD26 deficient (CD26 ) and wild-type mice (C57BL/6). The process of cutaneous wound healing was monitored on defined time schedule postwounding by macroscopic, microscopic, and biochemical analyses. Obtained results revealed a better rate of wound closure, revascularization and cell proliferation in CD26 mice, with enhanced local expression of hypoxia-inducible factor 1α and vascular endothelial growth factor. CD26 deficiency induced prompt macrophage recruitment at the site of skin damage but did not influence mobilization of T-cells in comparison with wild-type mice. CD26 mice have significantly higher values of IP-10 in serum and control skins compared with wild-type mice but values in wounds did not differ significantly on days 2, 4, and 7 of wound healing. DPP IV/CD26 activity was found to be decreased 4 days postwounding in serum and 2, 4, and 7 days postwounding in wounds of wild-type animals compared with control skins. These findings contribute to better understanding of wound healing mechanisms and could give a support in finding new therapeutic approaches for wound healing and tissue regeneration.

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Section: Discussionmentioning

confidence: 51%

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

Batičić

Pugel

Detel

et al. 2017

Wound Repair Regeneration

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“…In this context, the beneficial impact of stem cells on skin wound healing is evident, especially for the regeneration of blood vessels [41]. Stem cells or progenitor cells seem to support this process by multiple paracrine effects especially by high levels of pro-angiogenic molecules (i.e., VEGF, HGF, bFGF, EGF, TGF-β, IGF-1) [44,45,46,47]. These effects could be demonstrated in rodent diabetic wounding models, further underscoring the significant activity of stem cells and their potential in repair-resistant chronic wounds [45,46,48,49].…”

Section: Angiogenesis In Skin Wound Healingmentioning

confidence: 99%

Skin Wound Healing: An Update on the Current Knowledge and Concepts

Sorg

Tilkorn²,

Hager³

et al. 2016

Eur Surg Res

948

691

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Background: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. Methods: For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. Results: The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. Conclusion: Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown. The purpose of the following update on skin wound healing is to focus on the different phases and to brief the reader on the current knowledge and new insights. Skin wound healing is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications.

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“…VCAM1 was not expressed on the EC (Table 1). Since many chemokines are released at inflammation sites and are able to either inhibit or induce the angiogenic processes [34], we also determined the expression of a number of chemokine receptors (CXCR1, 2, 3, 4 and CCR2) (Table 1). With the exception of CXCR4, which was expressed on 29% of EC, all other chemokine receptors were expressed on less than 5% of the EC population.…”

Section: Resultsmentioning

confidence: 99%

Extensive Characterization and Comparison of Endothelial Cells Derived from Dermis and Adipose Tissue: Potential Use in Tissue Engineering

et al. 2016

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Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells as adipose tissue can easily be obtained by liposuction. Since adipose-EC are now gaining more interest in tissue engineering, we aimed to extensively characterize endothelial cells from adipose tissue (adipose-EC) and compare them with endothelial cells from dermis (dermal-EC). The amount of endothelial cells before purification varied between 4–16% of the total stromal population. After MACS selection for CD31 positive cells, a >99% pure population of endothelial cells was obtained within two weeks of culture. Adipose- and dermal-EC expressed the typical endothelial markers PECAM-1, ICAM-1, Endoglin, VE-cadherin and VEGFR2 to a similar extent, with 80–99% of the cell population staining positive. With the exception of CXCR4, which was expressed on 29% of endothelial cells, all other chemokine receptors (CXCR1, 2, 3, and CCR2) were expressed on less than 5% of the endothelial cell populations. Adipose-EC proliferated similar to dermal-EC, but responded less to the mitogens bFGF and VEGF. A similar migration rate was found for both adipose-EC and dermal-EC in response to bFGF. Sprouting of adipose-EC and dermal-EC was induced by bFGF and VEGF in a 3D fibrin matrix. After stimulation of adipose-EC and dermal-EC with TNF-α an increased secretion was seen for PDGF-BB, but not uPA, PAI-1 or Angiopoietin-2. Furthermore, secretion of cytokines and chemokines (IL-6, CCL2, CCL5, CCL20, CXCL1, CXCL8 and CXCL10) was also upregulated by both adipose- and dermal-EC. The similar characteristics of adipose-EC compared to their dermal-derived counterpart make them particularly interesting for skin tissue engineering. In conclusion, we show here that adipose tissue provides for an excellent source of endothelial cells for tissue engineering purposes, since they are readily available, and easily isolated and amplified.

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Chemokine Regulation of Angiogenesis During Wound Healing

Cited by 152 publications

References 48 publications

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

Skin Wound Healing: An Update on the Current Knowledge and Concepts

Extensive Characterization and Comparison of Endothelial Cells Derived from Dermis and Adipose Tissue: Potential Use in Tissue Engineering

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