The Regenerative Microenvironment of the Tissue Engineering for Urethral Strictures.

Urethral stricture caused by various reasons has threatened the quality of life of patients for decades. Traditional reconstruction methods, especially for long-segment injuries, have shown poor outcomes in treating urethral strictures. Tissue engineering for urethral regeneration is an emerging concept in which special designed scaffolds and seed cells are used to promote local urethral regeneration. The scaffolds, seed cells, various factors and the host interact with each other and form the regenerative microenvironment. Among the various interactions involved, vascularization and fibrosis are the most important biological processes during urethral regeneration. Mesenchymal stem cells and induced pluripotent stem cells play special roles in stricture repair and facilitate long-segment urethral regeneration, but they may also induce carcinogenesis and genomic instability during reconstruction. Nevertheless, current technologies, such as genetic engineering, molecular imaging, and exosome extraction, provide us with opportunities to manage seed cell-related regenerative risks. In this review, we described the interactions among seed cells, scaffolds, factors and the host within the regenerative microenvironment, which may help in determining the exact molecular mechanisms involved in urethral stricture regeneration and promoting clinical trials and the application of urethral tissue engineering in patients suffering from urethral stricture.

Adipose stem cells in tissue regeneration and repair: From bench to bedside.

ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the "ADSCs-scaffold composite" into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.

Identification of a copper metabolism-related gene signature for predicting prognosis and immune response in glioma.

BACKGROUND: Gliomas are highly refractory intracranial cancers characterized by genetic and transcriptional heterogeneity. However, therapeutic options are limited. In the last years, copper-induced cell death is becoming a prospective treatment strategy for gliomas and other solid tumors, but copper metabolism-related genes associated with cancer development remain unclear. METHODS: We first collected gene expression data from The Cancer Genome Atlas (TCGA) to identify significantly differentially expressed copper metabolism-related genes in gliomas. Using these genes, we performed COX regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression to construct the prognostic model. The prognostic value of the model was further validated by CGGA testing set. Subsequently, functional analyses were carried out, including gene set enrichment analysis (GSEA), immune infiltration analysis, and mutation analysis. Finally, the expression levels of these genes were verified by immunohistochemical analysis. RESULTS: The prognostic model consisted of 7 genes: CDK1, LOXL2, LOXL3, NFE2L2, SLC31A1, SUMF1 and FDX1. According to this prognosis model, glioma patients could be split into the high-risk group or low-risk group, and the low-risk group showed significantly better prognostic survival (p < 0.001). Moreover, the high-risk group had higher levels of immune cell infiltration, immune checkpoint genes expression, and higher tumor mutational burden (TMB), which indicates that they might benefit more from immunotherapy. Finally, we confirmed the expression level of FDX1, SUMF1, and SLC31A1 protein as significantly different in glioblastoma, lower-grade glioma, and non-tumor brain tissues by immunohistochemical analysis, and the high expression of FDX1 and SLC31A1 protein was related to poor survival in glioma patients. CONCLUSIONS: Our study could contribute to the prognosis prediction and decision-making in patients with gliomas.