Updates in wound healing: Mechanisms and translation

Eming, Sabine A.; Tomic‐Canic, Marjana

doi:10.1111/exd.13281

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…In vitro studies have shown that primary cells isolated from chronic wounds maintain tissue characteristics and show altered proliferative and migratory capacity accompanied with an inability to respond to wound‐healing stimuli such as growth factors and cytokines . While the actions of multiple cell types are tightly regulated by growth factors, cytokines and signalling molecules during the acute wound‐healing process, this regulation, and interplay between different signalling factors, is dysregulated in chronic wounds . Furthermore, chronic wounds exhibit high levels of metalloproteinases (MMP) and a perturbed ratio between MMP and tissue inhibitors of metalloproteinases (TIMPs), which contribute to a hostile wound environment, lack of growth factor and cytokine signalling and subsequently delayed healing (Table ) .…”

Section: What Did We Learn So Far From Studies Utilizing Human Wound mentioning

confidence: 99%

“…[51,52,55,62,63] While the actions of multiple cell types are tightly regulated by growth factors, cytokines and signalling molecules during the acute wound-healing process, [64][65][66] this regulation, and interplay between different signalling factors, is dysregulated in chronic wounds. [4,36,67,68] Furthermore, chronic wounds exhibit high levels of metalloproteinases (MMP) and a perturbed ratio between MMP and tissue inhibitors of metalloproteinases (TIMPs), which contribute to a hostile wound environment, lack of growth factor and cytokine signalling and subsequently delayed healing ( Table 2). [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] In-depth characterization of VLU wound edge tissue has revealed a loss of the epidermal stem cells niche, deregulation of epidermal differentiation and activation of β-catenin pathway coupled with attenuation of TGFβ and epidermal growth factor (EGF) signalling pathways.…”

Section: What D Id We Le Arn So Far From S Tud Ie S Utilizing H Umamentioning

confidence: 99%

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Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

Pastar

Wong

Egger

et al. 2018

Experimental Dermatology

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The clinical field of wound healing is challenged by numerous hurdles. Not only are wound-healing disorders complex and multifactorial, but the corresponding patient population is diverse, often elderly and burdened by multiple comorbidities such as diabetes and cardiovascular disease. The care of such patients requires a dedicated, multidisciplinary team of physicians, surgeons, nurses and scientists. In spite of the critical clinical need, it has been over 15 years since a treatment received approval for efficacy by the FDA in the United States. Among the reasons contributing to this lack of effective new treatment modalities is poor understanding of mechanisms that inhibit healing in patients. Additionally, preclinical models do not fully reflect the disease complexity of the human condition, which brings us to a paradox: if we are to use a "mechanistic" approach that favours animal models, we can dissect specific mechanisms using advanced genetic, molecular and cellular technologies, with the caveat that it may not be directly applicable to patients. Traditionally, scientific review panels, for either grant funding or manuscript publication purposes, favour such "mechanistic" approaches whereby human tissue analyses, deemed "descriptive" science, are characterized as a "fishing expedition" and are considered "fatally flawed." However, more emerging evidence supports the notion that the use of human samples provides significant new knowledge regarding the molecular and cellular mechanisms that control wound healing and contribute to inhibition of the process in patients. Here, we discuss the advances, benefits and challenges of translational research in wound healing focusing on human subject research.

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Section: What Did We Learn So Far From Studies Utilizing Human Wound mentioning

confidence: 99%

Section: What D Id We Le Arn So Far From S Tud Ie S Utilizing H Umamentioning

confidence: 99%

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

Pastar

Wong

Egger

et al. 2018

Experimental Dermatology

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“…The management of chronic skin ulcers constitutes a major healthcare challenge [ 6 , 16 ], which is exacerbated by the increasing prevalence of vascular perfusion disorders, diabetes mellitus and other conditions associated with impaired-wound healing. Therefore, novel treatment strategies for chronic skin wounds need to be urgently developed and tested; ideally in the human system.…”

Section: Introductionmentioning

confidence: 99%

Nestin+ progenitor cells isolated from adult human sweat gland stroma promote reepithelialisation and may stimulate angiogenesis in wounded human skin ex vivo

et al. 2019

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The combination of an aging population and an increasing prevalence of diseases associated with impaired-wound healing, including obesity, peripheral vascular disease and diabetes, is likely to result in a dramatic increase in the incidence and prevalence of chronic skin wounds. Indeed, systemic reviews are now not only trying to establish both the prevalence and the often under-estimated socio-economic costs of chronic skin wounds, but most importantly are addressing the impact that chronic wounds have on quality of life. Given the clear need for novel approaches to the management of chronic skin ulceration, ideally developed and tested in the human system in a manner that can be rapidly translated into clinical practice, we examined the effects of multipotent primary human nestin + progenitor cells on human wound healing in an ex vivo model. Human sweat gland-derived nestin + cells demonstrated the capacity to significantly promote two key wound healing parameters, i.e., both reepithelialisation and angiogenesis in experimentally wounded, organ-cultured human skin. The current data further support the use of full-thickness human skin wound-healing models ex vivo to pre-clinically test wound healing-promoting candidate agents. Whilst larger studies are required to substantiate a firm “proof-of-concept,” our preliminary studies encourage further efforts to systemically determine the potential of cell-based regenerative medicine strategies in general, and the use of skin appendage-associated human nestin + cells in particular, as novel treatment strategies for chronic skin ulceration. Electronic supplementary material The online version of this article (10.1007/s00403-019-01889-x) contains supplementary material, which is available to authorized users.

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“…The mechanism underlying epithelial tissue healing and pathologies, such as failure to repair, are not fully understood. This is an important topic in basic biomedical research since it involves a fundamental principle of survival [8]. An oral mucosal wound healing model was chosen because it nearly always shows superior wound healing when compared with other tissues.…”

Section: Introductionmentioning

confidence: 99%

Laser Capture Microdissection of Epithelium from a Wound Healing Model for MicroRNA Analysis

et al. 2018

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MicroRNAs are ~22 nucleotide-long noncoding RNAs influencing many cellular processes (including wound healing) by their regulatory functions on gene expression. The ability to analyze microRNA in different cells at the wound site is essential for understanding the critical role(s) of microRNA during various phases of wound healing. Laser capture micro-dissection (LCM) is an effective method to distinguish between relevant and non-relevant cells or tissues and enables the researcher to obtain homogeneous, ultra-pure samples from heterogeneous starting material. We present here our protocol for procuring epithelial cells from a mouse wound healing model using a Leica LMD7000 Laser Microdissection system, as well as the RNA isolation and downstream microRNA analysis. Using this method, researchers can selectively and routinely analyze regions of interest down to single cells to obtain results that are relevant, reproducible, and specific.

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Updates in wound healing: Mechanisms and translation

Cited by 15 publications

References 19 publications

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

Nestin+ progenitor cells isolated from adult human sweat gland stroma promote reepithelialisation and may stimulate angiogenesis in wounded human skin ex vivo

Laser Capture Microdissection of Epithelium from a Wound Healing Model for MicroRNA Analysis

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