Keloids are an excessive tissue response to dermal damage, characterized by uncontrolled growth and a high recurrence rate after various treatments. Abnormalities with the extracellular matrix (ECM) are one of the most important contributing factors to the formation of keloids. Although exosomes from human adipose-derived mesenchymal stem cells (adMSC-Exos) have been shown to promote repair and regeneration in wounds, they have seldom been studied for the treatment of keloids. In this study, we aimed to investigate the effects of adMSC-Exos on ECM remodeling in keloids using both in vitro and ex vivo models. The results showed that adMSC-Exos inhibited gene and protein expression of collagen I (COL-1), collagen III (COL-3), fibronectin (FN), and α-smooth muscle actin (α-SMA) in keloid fibroblasts (KFs). Furthermore, using an ex vivo tissue explant model, we found that adMSC-Exos significantly suppressed COL production and disrupted the microvessel stucture. We also demonstrated that adMSC-Exos inhibited the protein expression of Smad3 and Notch-1, and the expression of transforming growth factor β2 (TGF-β2) in KFs, and promoted the expression of TGF-β3. These findings largely explain the mechanisms underlying the inhibition of ECM production in keloids by adMSC-Exos. In conclusion, our results revealed that adMSC-Exos effectively inhibited the production of ECM in keloids, which provides a new potential alternative for the systemic treatment of keloids. Graphical abstract

Aim: This study was conducted to reveal epigenetic landscape in infantile hemangiomas (IHs) and identify transcription factors (TFs) and their downstream genes active in IHs. Materials & methods: W...

The current assay aimed to fabricate and analyze a potent wound healing structure based on a naringin (Nar)/β-cyclodextrin (β-CD)-loaded chitosan hydrogel. Using the simulation studies, we assessed the interactions among the Nar, β-CD, and the formation of the inclusion complex. Then, the formation of the hydrogel nanocomplex was simulated and evaluated using the in silico methods. The results showed that after optimization of the structures by DMol3 based on DFT-D, the total energies of Nar, GP, CD, and β-CD were calculated at −2100.159, −912.192, −3778.370, and −4273.078 Ha, respectively. The encapsulation energy of Nar on β-CD in the solvent phase was calculated at −93.626 kcal/mol, and the Nar structure was located inside β-CD in solution. The negative interaction energy value for the encapsulation of Nar on β-CD suggests the exothermic adsorption process and a stable structure between Nar and β-CD. Monte Carlo method was applied to obtain adsorption of CS/GP on Nar/β-CD. Its value of the obtained interaction energy was calculated at −1.423 × 103 kcal/mol. The characterization confirmed the formation of a Nar/β-CD inclusion complex. The Zeta potential of the pristine β-CD changed from −4.60 ± 1.1 to −17.60 ± 2.34 mV after interaction with Nar, and the heightened surface negativity can be attributed to the existence of electron-rich naringin molecules, as well as the orientation of the hydroxyl (OH) group of the β-CD toward the surface in an aqueous solution. The porosity of the fabricated hydrogels was in the range of 70–90% and during 14 days around 47.0 ± 3.1% of the pure hydrogel and around 56.4 ± 5.1 of hydrogel nanocomposite was degraded. The MTT assay showed that the hydrogels were biocompatible, and the wound contraction measurement (in an animal model) showed that the closure of the induced wound in the hydrogel nanocomposite treatment was faster than that of the control group (wound without treatment). The results of this study indicate that the developed bioactive wound healing 3D structure, which is composed of a chitosan hydrogel containing a Nar/β-CD inclusion nanocomplex, has potential as an effective material for wound dressing applications.

Bone repair using tissue‐engineered bone (TEB) in a large defect or accompanied by a poor recipient vascular bed is a long‐standing challenge. Surgical vascular carrier patterns of vascular bundle (VB) and arteriovenous loop (AV loop) have been shown to improve the vascularization and repair capacity of TEB. However, the effects of these different vascular carrier patterns on angiogenesis and osteogenesis in TEB have never been evaluated. Here, TEB was constructed with bone marrow mesenchymal stem cells (BMSCs) and β‐TCP and prevascularized by the VB or AV loop technique in beagle dogs. The vascularization and bone formation in TEB were quantitatively compared using Microfil perfusion, histological examination and CT and micro‐CT analyses. The distribution and constitution of the neovasculature were analysed to determine the underlying mechanism of angiogenesis. The results showed that prevascularized TEB generated bone tissue faster and more homogeneously than untreated TEB. The VB technique was found to strike a better balance between bone regeneration and β‐TCP scaffold degradation than the AV loop strategy, which resulted in more vascularization but less bone yield, due to faster degradation of the β‐TCP scaffold. This study indicates that a suitable triangular relationship, composed of bone regeneration, scaffold degradation and vasculature, is critical to TEB construction. Copyright © 2015 John Wiley & Sons, Ltd.

Purpose: Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications. M2-polarized macrophages in IHs promote disease progression. In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs. Patients and Methods: Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs. Results: M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway. Conclusion: MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.

Infantile hemangiomas are common vascular tumors with a specific natural history. The proliferation and regression mechanism of infantile hemangiomas may be related to the multilineage differentiation ability of hemangioma stem cells, but the specific mechanism is not well elucidated. KIAA1429 is an N⁶‐methyladenosine methylation‐related protein that can also exert its role in a methylation‐independent manner. This study aims to explore the function of KIAA1429 in infantile hemangiomas. qRT‐PCR, western blotting, and immunostaining were performed to verify the expression of KIAA1429. The endothelial and fibroblast‐like phenotypes of hemangioma endothelial cells were detected after KIAA1429 knockdown and overexpression. The stemness properties of hemangioma endothelial cells and the underlying mechanism of KIAA1429 in hemangiomas were also investigated. Nude mouse models of infantile hemangiomas were conducted to ascertain the effects of KIAA1429 in vivo. The results showed that KIAA1429 was highly expressed in infantile hemangiomas, particularly in involuting hemangiomas. In vitro experiments confirmed that KIAA1429 inhibited the endothelial phenotype, enhanced the differentiation ability, and promoted the fibroblast‐like phenotype of hemangioma endothelial cells by inducing endothelial cell transition to facultative stem cells. However, the effect of KIAA1429 on the potential target was shown to be independent of N⁶‐methyladenosine methylation modification. Mouse models further revealed that KIAA1429 could inhibit the proliferation and promote the regression of hemangiomas. In conclusion, this study found that KIAA1429 played an important role in the regression of infantile hemangiomas by enhancing the stemness of hemangioma endothelial cells and could be a potential treatment target for infantile hemangiomas.