Exposure of Human Skin Organoids to Low Genotoxic Stress Can Promote Epithelial-to-Mesenchymal Transition in Regenerating Keratinocyte Precursor Cells

Cavallero, Sophie; Granito, Renata Neves; Stockholm, Daniel; Azzolin, Peggy; Martin, Michèle; Fortunel, Nicolas O.

doi:10.3390/cells9081912

Cited by 8 publications

(6 citation statements)

References 37 publications

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“… 33 , 34 Consistent with these previous findings, in the present study, DHA inhibited the formation of HS via the inhibition of α-SMA, survivin and collagen I. Additionally, it has been reported that the activation of α-SMA promotes the epithelial-mesenchymal transition (EMT) process. 35 , 36 Based on the previous research, it can be hypothesized that DHA may act as an inhibitor of the EMT process.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Wang

Song

Zhang

et al. 2021

DDDT

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Background The formation of hypertrophic scars (HS) can result in the failure of glaucoma surgery, and fibrosis is known to be closely associated with the progression of HS. Dihydroartemisinin (DHA) has been reported to inhibit the progression of fibrosis; however, whether DHA can alleviate the formation of HS remains unclear. Methods In the present study, in order to examine the effects of DHA on the progression of HS, human Tenon’s capsule fibroblasts (HTFs) were isolated from patients who underwent glaucoma surgery. In addition, Western blot analysis, microtubule associated protein 1 light chain 3 α staining and reverse transcription-quantitative PCR were performed to detect protein and mRNA expression levels in the HTFs, respectively. Cell proliferation was detected by Ki67 staining. Flow cytometry was used to examine apoptosis and reactive oxygen species (ROS) levels in the HTFs. Results The results revealed that TGF-β promoted the proliferation and fibrosis of HTFs; however, DHA significantly reversed the effects of TGF-β by increasing cell autophagy. In addition, DHA notably induced the apoptosis of TGF-β-stimulated HTFs by increasing the ROS levels, while these increases were partially reversed by 3-methyladenine. Furthermore, DHA notably increased the expression of microRNA (miR)-145-5p in HTFs in a dose-dependent manner. Conclusion The present study demonstrated that DHA inhibits the TGF-β-induced fibrosis of HTFs by inducing autophagy. These findings may aid in the development of novel agents for the prevention of the formation of HS following glaucoma surgery.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Wang

Song

Zhang

et al. 2021

DDDT

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“…Assessment of keratinocyte polarity was performed in reconstructed epidermis as previously described [ 19 ]. Briefly, regions of interest (ROI) were defined in tissue sections stained with DAPI, corresponding to ~600 µm section length (20 images per condition).…”

Section: Methodsmentioning

confidence: 99%

Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro

Domingues

Darle

Masson

et al. 2022

Cells

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Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as a consequence of a prolonged inflammatory phase during the healing process. They are extremely hard to heal and persist as a significant health care problem due to the absence of effective treatment and the uprising number of patients. Indeed, there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds. Development in skin engineering leads to a small catalogue of available substitutes manufactured in Good Manufacturing Practices compliant (GMPc) conditions. Those substitutes are produced using primary cells that could limit their use due to restricted sourcing. Here, we propose GMPc protocols to produce functional populations of keratinocytes and fibroblasts derived from pluripotent stem cells to reconstruct the associated dermo-epidermal substitute with plasma-based fibrin matrix. In addition, this manufactured composite skin is biologically active and enhances in vitro wounding of keratinocytes. The proposed composite skin opens new perspectives for skin replacement using allogeneic substitute.

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“…In another study, low-dose γ-irradiation was applied to skin substitutes prior to transplantation onto nude mice, resulting in focal dysplasia in xenografted epidermises and exhibiting characteristics of epithelial-to-mesenchymal transition (EMT). This study highlighted that even minimal radiation stress during the regeneration of keratinocyte stem and precursor cells can create a microenvironment that may promote long-term carcinogenesis [ 42 ]. Additionally, investigating the effects of environmental factors, such as air pollution and cigarette smoking, on skin aging and related diseases is both feasible and necessary using in vitro treated skin organoids.…”

Section: Applications and Prospectsmentioning

confidence: 99%

Bioengineered skin organoids: from development to applications

Hong,

Zhu,

et al. 2023

Military Med Res

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Significant advancements have been made in recent years in the development of highly sophisticated skin organoids. Serving as three-dimensional models that mimic human skin, these organoids have evolved into complex structures and are increasingly recognized as effective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional systems and ethical concerns. The inherent plasticity of skin organoids allows for their construction into physiological and pathological models, enabling the study of skin development and dynamic changes. This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages. Furthermore, it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques, such as 3D printing and microfluidic devices. The review also summarizes and discusses the diverse applications of skin organoids in developmental biology, disease modelling, regenerative medicine, and personalized medicine, while considering their prospects and limitations.

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Exposure of Human Skin Organoids to Low Genotoxic Stress Can Promote Epithelial-to-Mesenchymal Transition in Regenerating Keratinocyte Precursor Cells

Cited by 8 publications

References 37 publications

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro

Bioengineered skin organoids: from development to applications

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