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

Propranolol has been widely used in treating infantile hemangiomas (IHs). But recurrence of IHs was found in some cases on cessation of propranolol treatment. The other is that Chinese individuals reacted to propranolol differently from American Whites. Whether the difference of sensitivity is due to the β adrenoceptor (β-AR) expression pattern of hemangioma initiating cells remains unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs) from proliferative IHs and analyzed the biological characteristics and β-AR expression pattern of hemSCs by immunostaining, Western blotting and multilineage differentiation assay as well. We also tested the effects of propranolol on hemSCs by evaluating VEGF expression, proliferation and apoptosis related parameters. Our results indicated that CD133(+) hemSCs located pre-vascular in proiferative IH tissues. Both β1 and β2-AR were expressed, while β2-AR was dominant on hemSCs. Propranolol at 100-150 μM inhibited proliferation of hemSCs, not did 50 μM. Propranolol down-regulated VEGF expression of hemSCs, instead of inducing apoptosis. The adipogenic potential was enhanced by propranolol. Therefore, our current results suggested propranolol could not induce apoptosis of hemSCs, but played a curative role though suppressing VEGF synthesis and enhancement of adipogenesis of hemSCs. Our results might partially provide the insight of mechanism of relapse in some cases on cessation of propranolol treatment.

Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.

We aimed to evaluate the efficacy of combination of propranolol and sclerotherapy in treating parotid hemangiomas. Twenty-six parotid hemangiomas patients were subjected to combined treatment from January 2009 and June 2014. The effects of the therapy modality were evaluated. Nineteen patients were females and 7 were males. The median age of treatment initiation was 4.96 months. Twelve lesions were located on the left side parotid glands, while thirteen lesions affected the right side. One infant had bilateral lesions. One to six (average 2.04) injections were performed and the mean period for propranolol was 8.94 months. All the patients got satisfied aesthetic outcomes. No complications of propranolol or sclerotherapy occurred during the whole medication period. The study demonstrated that combination of propranolol and sclerotherapy was an effective and safe method for infantile parotid hemangiomas. Larger-scale studies should be performed to further investigate the long-term efficacy and results of the present combined method for infantile parotid hemangiomas.

Combination of propranolol and sclerotherapy for treatment of infantile parotid hemangiomas.

Under septic conditions, Lipopolysaccharide (LPS)-induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein-3'-sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro-protective effects through its anti-apoptotic property. However, whether GSS protects against sepsis-induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS-induced Myd88/NF-κB/BCL-2 signalling pathway activation and subsequent EC apoptosis were effectively down-regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis-induced BCL-2 changes in expression in mouse lungs but also blocked sepsis-associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on Myd88/NF-κB/BCL-2 signalling in lung ECs.

Genistein-3'-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling.

. Under septic conditions, LPS induced lung vascular endothelial cell (EC) injury, and the release of inflammatory mediator launches and aggravates acute lung injury (ALI). There are no effective therapeutic options for ALI. Genistein-3'-sodium sulfonate (GSS) is a derivative of native soy isoflavone, which exhibits neuroprotective effects via its antiapoptosis property. However, whether GSS protect against sepsis-induced EC injury and release of inflammatory mediators has not been determined. In this study, we found that GSS not only downregulated the levels of TNF- and IL-6 in the lung and serum of mice  but also inhibited the expression and secretion of TNF- and IL-6 in ECs. Importantly, we also found that GSS blocked LPS-induced TNF- and IL-6 expression in ECs via the Myd88/NF-B signaling pathway. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on inflammatory response in lung ECs.

Suppressive Effects of GSS on Lipopolysaccharide-Induced Endothelial Cell Injury and ALI via TNF- and IL-6.

Quick and effective sterilization of drug-resistant bacteria inevitably became an ever-growing global challenge. In this study, a multifunctional composite (PDA/Cu-CS) hydrogel mainly composed of polydopamine (PDA) and copper-doped calcium silicate ceramic (Cu-CS) was prepared. It was confirmed that PDA/copper (PDA/Cu) complexing in the composite hydrogel played a key role in enhancing the photothermal performance and antibacterial activity. Through a unique "hot ions effect", created by the heating of Cu ions through the photothermal effect of the composite hydrogel, the hydrogel showed high-efficiency, quick, and long-term inhibition of methicillin-resistant  and . In addition, the hydrogel possessed remarkable bioactivity to stimulate angiogenesis. The in vivo results confirmed that the "hot ions effect" of the composite hydrogel removed existing infection in the wound area efficiently and significantly promoted angiogenesis and collagen deposition during infectious skin wound healing. Our results suggested that the design of multifunctional hydrogels with "hot ions effect" may be an effective therapeutic approach for the treatment of infectious wounds.

PDA/Cu Bioactive Hydrogel with "Hot Ions Effect" for Inhibition of Drug-Resistant Bacteria and Enhancement of Infectious Skin Wound Healing.

Diabetic wounds significantly affect the life quality of patients and may cause amputation and mortality if poorly managed. Recently, a wide range of cell-based methods has emerged as novel therapeutic methods in treating diabetic wounds. Adipose-derived stem cells (ASCs) are considered to have the potential for widespread clinical application of diabetic wounds treatment in the future. This review summarized the mechanisms of ASCs to promote diabetic wound healing, including the promotion of immunomodulation, neovascularization, and fibro synthesis. We also review the current progress and limitations of clinical studies using ASCs to intervene in diabetic wound healing. New methods of ASC delivery have been raised in recent years to provide a standardized and convenient use of ASCs.

Adipose-Derived Stem Cells for the Treatment of Diabetic Wound: From Basic Study to Clinical Application.

Barley ( L.) grass has been recognized as a functional food with a wide spectrum of health-promoting properties. Supplementation with barley grass has the potential to prevent chronic diseases, such as cancer. Here, we investigated whether barley grass could protect against hepatocellular carcinoma (HCC). Our data showed that administration of barley grass juice attenuates tumor development in a hydrodynamic gene delivery-induced model of HCC. The expression levels of the immune cell markers  and  were upregulated in the barley grass juice-treated and normal groups, compared to those in the vehicle group in the HCC model. Immune cells (CD45+, F4/80+, and CLEC4F + iNOS + cells) infiltration in the liver increased following barley grass juice administration. Our results indicate that barley grass could be beneficial for HCC alleviation, partly by regulating immune cell infiltration. The ingredients of barley grass affect immune cell infiltration in HCC, and the detailed mechanism requires further study.

Barley Grass Juice Attenuates Hydrodynamic Transfection-Induced HCC Initiation in Mice.

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.

The reconstruction of large-sized soft tissue defects remains a substantial clinical challenge, with adipose tissue engineering emerging as a promising solution. The acellular dermal matrix (ADM), known for its intricate spatial arrangement and active cytokine involvement, is widely employed as a scaffold in soft tissue engineering. Since ADM shares high similarity with decellularized adipose matrix, it holds potential as a substitute for adipose tissue. This study explores the adipogenic ability of a spongy material derived from ADM via vacuum-thermal crosslinking (T-ADM), characterized by high porosity, adjustable thickness, and suitable mechanical strength. Adipose-derived stem cells (ADSCs) are considered ideal seed cells in adipose tissue engineering. Nevertheless, whether pre-adipogenic induction is necessary before their incorporation remains debatable. In this context, ADSCs, both with and without pre-adipogenic induction, were seeded into T-ADM to regenerate vascularized adipose tissue. A comparative analysis of the two constructs was performed to evaluate angiogenesis and adipogenesis, and tissue regeneration efficacy. Additionally, RNA-seq analysis was utilized to investigate the potential mechanisms. The results showed that T-ADM exhibited good performance in terms of volume retention and maintenance of adipocyte phenotype, confirming its suitability as a scaffold for adipose tissue engineering.outcomes demonstrated that pre-adipogenic induction enhanced the adipogenic level of ADSCs, but reduced their ability to promote vascularization. Furthermore, constructs utilizing pre-induced ADSCs showed an insignificant superiority infat formation, and neovascularization compared with those with non-induced ADSCs, which may be attributed to similar macrophage regulation, and balanced modulation of the proliferator-activated receptor-and hypoxia-inducible factor 1pathways. Consequently, the direct use of ADSCs is advocated to streamline the engineering process and reduce associated costs. The combined strategy of T-ADM with ADSCs proves to be feasible, convenient and effective, offering substantial potential for addressing large-sized tissue deficits and facilitating clinical applications.

Thermal-crosslinked acellular dermal matrix combined with adipose-derived stem cells to regenerate vascularized adipose tissue.

Defects in the posterior lamella of the eyelid are prevalent in the clinical settings, which comprises the tarsal plate and conjunctiva and has limited regenerative capacity. Currently, homogenous scaffolds are used for repair, but they fail to recapitulate the natural bilayer structure and reepithelialization. In this study, we designed a bilamellar scaffold (bGA-ADM) with a heterogeneous structure to repair such defects and promote the integrated regeneration of tarso-conjunctival composite tissue.

Article	Year
Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells. International journal of clinical and experimental pathology\| PubMed ID: 25120757	2014
Combination of propranolol and sclerotherapy for treatment of infantile parotid hemangiomas. International journal of clinical and experimental medicine\| PubMed ID: 26379880	2015
Genistein-3'-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling. Journal of cellular and molecular medicine\| PubMed ID: 31756053	2020
Suppressive Effects of GSS on Lipopolysaccharide-Induced Endothelial Cell Injury and ALI via TNF- and IL-6. Mediators of inflammation\| PubMed ID: 32082076	2019
PDA/Cu Bioactive Hydrogel with "Hot Ions Effect" for Inhibition of Drug-Resistant Bacteria and Enhancement of Infectious Skin Wound Healing. ACS applied materials & interfaces\| PubMed ID: 32530593	2020
Adipose-Derived Stem Cells for the Treatment of Diabetic Wound: From Basic Study to Clinical Application. Frontiers in endocrinology\| PubMed ID: 35898452	2022
Barley Grass Juice Attenuates Hydrodynamic Transfection-Induced HCC Initiation in Mice. Nutrition and cancer\| PubMed ID: 36495148	2023
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
Thermal-crosslinked acellular dermal matrix combined with adipose-derived stem cells to regenerate vascularized adipose tissue. Biomedical materials (Bristol, England)\| PubMed ID: 39879651	2025
Heterogeneous-structural bilamellar bionic scaffold for integrated regeneration of tarso-conjunctival composite tissue. Journal of translational medicine\| PubMed ID: 41715185	2026

Mengling Chang

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