Human Wound Healing Ex Vivo Model with Focus on Molecular Markers

Gherardini, Jennifer; Lessen, Max van; Piccini, Ilaria; Edelkamp, Janin; Bertolini, Marta

doi:10.1007/978-1-0716-0648-3_21

Cited by 4 publications

(2 citation statements)

References 15 publications

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“…In order to ask whether type 2 cytokines alone suffice to induce early AD‐associated changes in healthy, non‐atopic human skin ex vivo, full‐thickness human skin was organ‐cultured in serum‐free medium 31 in the presence of rhIL‐4 and rhIL‐13 or vehicle for 24–120 h.…”

Section: Methodsmentioning

confidence: 99%

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Keren

Reich

Bertolini

et al. 2023

Allergy

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Background:The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo. Methods: Healthy human skin from non-atopic donors was transplanted onto SCID/ beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption. Results: Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress. Conclusions: This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.

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Section: Methodsmentioning

confidence: 99%

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Keren

Reich

Bertolini

et al. 2023

Allergy

Self Cite

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“…To examine potential effects of the patch on human wound healing, we inflicted 6 mm punch biopsy wounds on panniculectomy derived discarded skin kept in cell culture conditions (51,52) and monitored healing over four days (Fig. 8A and B).…”

Section: Application On a Human Ex Vivo Model Of Wound Healingmentioning

confidence: 99%

Strain-Programmable Patch for Diabetic Wound Healing

Theocharidis

Yuk

Roh

et al. 2021

Preprint

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Chronic wounds with impaired healing capability such as diabetic foot ulcers (DFU) are devastating complications in diabetic patients, inflicting rapidly growing clinical and economic burdens in aging societies. Despite recent advances in therapeutic approaches, limited benefits of the existing solutions highlight the critical need for novel therapeutic solutions for diabetic wound healing. Here we propose a strain-programmable patch capable of rapid robust adhesion on and programmable mechanical contraction of wet wounded tissues over days to offer a new therapeutic platform for diabetic wounds. The strain-programmable patch, consisting of a dried bioadhesive layer and a pre-stretched elastomer backing, implements a hydration-based shape-memory mechanism to achieve both uniaxial and biaxial contractions and stress remodeling of wet wounds in a programmable manner. We develop theoretical and numerical models to rationally guide the strain-programming and mechanical modulation of wounds. In vivo rodent and ex vivo human skin culture models validate the programmability and efficacy of the proposed platform and identify mechanisms of action for accelerated diabetic wound healing.

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A cyclic heptapeptide-based hydrogel boosts the healing of chronic skin wounds in diabetic mice and patients

Sun

et al. 2022

NPG Asia Mater

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The combined use of peptides, nanomaterials, and hydrogels is a promising strategy for chronic skin wound healing, which remains a huge clinical challenge. Here, we optimized the RL-QN15 peptide, which was shown to be a pro-healing drug candidate in our previous research, to obtain the cyclic heptapeptide (CyRL-QN15) with considerable therapeutic potency against skin wounds. Furthermore, a Zn2+-crosslinked sodium alginate (ZA) hydrogel containing hollow polydopamine (HPDA) nanoparticles loaded with CyRL-QN15 (HPDAlCyRL-QN15/ZA hydrogel) was prepared and characterized, which significantly enhanced the pro-healing potency of CyRL-QN15. At the cellular level, this nontoxic hydrogel accelerated the proliferation, migration, tube formation, and scratch healing of skin cells, regulated the secretion of cytokines from macrophages, directly scavenged free radicals, and decreased reactive oxygen species. Moreover, the HPDAlCyRL-QN15/ZA hydrogel significantly accelerated the healing of full-thickness skin wounds in type 2 diabetic mice by promoting the transition of macrophages to the M2 phenotype to reduce inflammation and cause re-epithelialization, formation of granulation tissue, deposition of collagen, and angiogenesis. Of note, the hydrogel also facilitated wound healing of diabetic patient skin cultured ex vivo. Overall, the HPDAlCyRL-QN15/ZA hydrogel presents a novel therapeutic strategy for clinical chronic skin wound (diabetic ulcer) healing.

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Human Wound Healing Ex Vivo Model with Focus on Molecular Markers

Cited by 4 publications

References 15 publications

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Strain-Programmable Patch for Diabetic Wound Healing

A cyclic heptapeptide-based hydrogel boosts the healing of chronic skin wounds in diabetic mice and patients

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