development-an-efficient-murine-tissue-expansion-model-for-skin

Development of an Efficient Murine Tissue Expansion Model for Skin Regeneration Research

Skin regeneration is essential for the healing of various superficial wounds and can be promoted by mechanical stimulation. Tissue expansion is a widely ...

Shanghai Jiaotong University School of Medicine

Hypertrophic scar (HS) formation is a skin fibroproliferative disease that occurs following a cutaneous injury, leading to functional and cosmetic impairment. To date, few therapeutic treatments exhibit satisfactory outcomes. The mechanical force has been shown to be a key regulator of HS formation, but the underlying mechanism is not completely understood. The Piezo1 channel has been identified as a novel mechanically activated cation channel (MAC) and is reportedly capable of regulating force-mediated cellular biological behaviors. However, the mechanotransduction role of Piezo1 in HS formation has not been investigated. In this work, we found that Piezo1 was overexpressed in myofibroblasts of human and rat HS tissues. In vitro, cyclic mechanical stretch (CMS) increased Piezo1 expression and Piezo1-mediated calcium influx in human dermal fibroblasts (HDFs). In addition, Piezo1 activity promoted HDFs proliferation, motility, and differentiation in response to CMS. More importantly, intradermal injection of GsMTx4, a Piezo1-blocking peptide, protected rats from stretch-induced HS formation. Together, Piezo1 was shown to participate in HS formation and could be a novel target for the development of promising therapies for HS formation.

Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1.

Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly used surgical method. However, the procedure's efficacy is often hindered by anatomical and histologic characteristics and blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of noncompliance to medical instructions. The purpose of this study was to explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders.

Acellular Dermal Matrix-Assisted Tissue Expansion for Giant Congenital Melanocytic Nevi of the Extremities and Trunk in Pediatric Patients.

Hypertrophic scarring is a fibro-proliferative disorder caused by abnormal cutaneous wound healing. Circulating metabolites and the gut microbiome may be involved in the formation of these scars, but high-quality evidence of causality is lacking. To assess whether circulating metabolites and the gut microbiome contain genetically predicted modifiable risk factors for hypertrophic scar formation. Two-sample Mendelian randomization (MR) was performed using MR-Egger, inverse-variance weighting (IVW), Mendelian Randomization Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median methods. Based on the genome-wide significance level, genetically predicted uridine (P = 0.015, odds ratio [OR] = 1903.514, 95% confidence interval [CI] 4.280-846,616.433) and isovalerylcarnitine (P = 0.039, OR = 7.765, 95% CI 1.106-54.512) were positively correlated with hypertrophic scar risk, while N-acetylalanine (P = 0.013, OR = 7.98E-10, 95% CI 5.19E-17-0.012) and glycochenodeoxycholate (P = 0.021, OR = 0.021 95% CI 0.003-0.628) were negatively correlated. Gastranaerophilales and two unknown gut microbe species (P = 0.031, OR = 0.378, 95% CI 0.156-0.914) were associated with an decreased risk of hypertrophic scarring. Circulating metabolites and gut microbiome components may have either positive or negative causal effects on hypertrophic scar formation. The study provides new insights into strategies for diagnosing and limiting hypertrophic scarring.

The role of circulating metabolites and gut microbiome in hypertrophic scar: a two-sample Mendelian randomization study.

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

Chemotherapy affects the development of pathological scarring after general thoracic surgery in children.

Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma's pathogenesis.

Spatial transcriptomic analysis deciphers adipocyte-to-fibroblast transformation in bleomycin-induced murine skin fibrosis.

Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing. We found that the dominant fibroblast subgroup in keloids is mechanoresponsive group, which showed enhanced mechanotransduction and migration. This mechanoresponsive fibroblast subgroup is likely to be the key cell population and confer aggressive growth of keloids. The results also indicate that the endothelial cells and keratinocytes in keloid involve in endothelial-mesenchymal and epithelial-mesenchymal transitions. This study demonstrated the mechanoresponsive fibroblasts and multiple cellular mesenchymal processes could pave the way for further investigations into the keloid aggressiveness.

Article	Year
Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1. Cell death & disease\| PubMed ID: 33649312	2021
Acellular Dermal Matrix-Assisted Tissue Expansion for Giant Congenital Melanocytic Nevi of the Extremities and Trunk in Pediatric Patients. Plastic and reconstructive surgery\| PubMed ID: 38546404	2025
The role of circulating metabolites and gut microbiome in hypertrophic scar: a two-sample Mendelian randomization study. Archives of dermatological research\| PubMed ID: 38822918	2024
Chemotherapy affects the development of pathological scarring after general thoracic surgery in children. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society\| PubMed ID: 39169718	2024
Spatial transcriptomic analysis deciphers adipocyte-to-fibroblast transformation in bleomycin-induced murine skin fibrosis. Chinese medical journal\| PubMed ID: 39345020	2024
Single cell transcriptomics reveals the cellular heterogeneity of keloids and the mechanism of their aggressiveness. Communications biology\| PubMed ID: 39702490	2024

Shengzhou Shan

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