New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation

Lebonvallet, Nicolas; Laverdet, Betty; Miséry, Laurent; Desmoulière, Alexis; Girard, Dorothée

doi:10.1111/exd.13681

Cited by 43 publications

(63 citation statements)

References 96 publications

(123 reference statements)

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“…After cutaneous injury, progenitor cells migrate into areas of injury and differentiate into myofibroblasts, which generate force and contract wounds 30 . An increase in the density of myofibroblasts in tissue is implicated in excessive collagen deposition in some disease settings 3,31 . In addition, adoptive transfer of purified fibroblasts in lung fibrosis showed upregulation of α-SMA together with ECM genes in transferred cells 28,32 .…”

Section: Discussionmentioning

confidence: 99%

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

et al. 2020

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Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagenproducing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1-expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1-expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

et al. 2020

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“…Future work could address the lack of medical treatment options for re‐innervation of skin following burn injuries . One way to expand research in this area would be to investigate ‘bio‐active’ materials for skin tissue replacements or in vitro skin tissue models which enhance healing, regrowth of neural cells, and also include or reintegrate vasculature . Bioprinting is another approach to create bio‐active skin with innervation and/or vascularization architectures within biomaterials, however, despite advances in skin bioprinting, such materials have yet to be developed for skin …”

Section: Discussionmentioning

confidence: 99%

The importance of the neuro‐immuno‐cutaneous system on human skin equivalent design

2019

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The skin is a highly complex organ, responsible for sensation, protection against the environment (pollutants, foreign proteins, infection) and thereby linked to the immune and sensory systems in the neuro‐immuno‐cutaneous (NIC) system. Cutaneous innervation is a key part of the peripheral nervous system; therefore, the skin should be considered a sensory organ and an important part of the central nervous system, an ‘active interface’ and the first connection of the body to the outside world. Peripheral nerves are a complex class of neurons within these systems, subsets of functions are conducted, including mechanoreception, nociception and thermoception. Epidermal and dermal cells produce signalling factors (such as cytokines or growth factors), neurites influence skin cells (such as via neuropeptides), and peripheral nerves have a role in both early and late stages of the inflammatory response. One way this is achieved, specifically in the cutaneous system, is through neuropeptide release and signalling, especially via substance P (SP), neuropeptide Y (NPY) and nerve growth factor (NGF). Cutaneous, neuronal and immune cells play a central role in many conditions, including psoriasis, atopic dermatitis, vitiligo, UV‐induced immunosuppression, herpes and lymphomas. Therefore, it is critical to understand the connections and interplay between the peripheral nervous system and the skin and immune systems, the NIC system. Relevant in vitro tissue models based on human skin equivalents can be used to gain insight and to address impact across research and clinical needs.

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“…Schwann cells, the glial cells of the peripheral nervous system (PNS), have received special attention because of their ability to support the regeneration of injured axons. [ ] Yet, recent discoveries have revealed important roles for SCs in non‐neural biology: gut homeostasis, [ ] stem cell maintenance, [ ] immune modulation, [ ] cutaneous wound healing [ ] and cancer progression. [ ] Given their abundance and distribution under the dermal‐epidermal junction, the question has been raised regarding their role in cutaneous homeostasis and neoplastic and inflammatory dermatoses.…”

Section: Introductionmentioning

confidence: 99%

Schwann cells as underestimated, major players in human skin physiology and pathology

Bray

Chéret

Yosipovitch

et al. 2019

Experimental Dermatology

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Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor‐like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial‐to‐mesenchymal‐like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.

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New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation

Cited by 43 publications

References 96 publications

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

The importance of the neuro‐immuno‐cutaneous system on human skin equivalent design

Schwann cells as underestimated, major players in human skin physiology and pathology

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