Rationale: Single-cell RNA sequencing (scRNA-seq) has provided an unbiased assessment of specific profiling of cell populations at the single-cell level. Conventional renal biopsy and bulk RNA-seq only average out the underlying differences, while the extent of chronic kidney transplant rejection (CKTR) and how it is shaped by cells and states in the kidney remain poorly characterized. Here, we analyzed cells from CKTR and matched healthy adult kidneys at single-cell resolution.

Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a promising alternative treatment for damaged or occlusive vessels. Large-scale tubular grafts, which can match arteries, arterioles, and venules, as well as meso- and microscale vasculature to alleviate ischemia or prevascularized engineered tissues, have been developed. In this review, materials and techniques for engineering tubular scaffolds and vasculature at all levels are discussed. Examples of vascularized tissue engineering in bone, peripheral nerves, and the heart are also provided. Finally, the current challenges are discussed and the perspectives on future developments in biofunctional engineered vessels are delineated.

Background: Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect, however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment.Results: We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated silent information regulator 1 (SIRT1) and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did.Conclusions: Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

Circular RNA (circRNA) is involved in the process of acute kidney injury (AKI), but only a few circRNAs have been reported. In the study, we investigated a new circRNA and its association with AKI....

Background: Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, which is a pathological injury caused by various chronic liver diseases. This study aimed to investigate the antifibrotic effects of BMSCs and elucidate the underlying mechanism by which BMSCs affect liver fibrosis in vitro and in vivo. Methods: After the rat liver fibrosis model was induced by continuous injection of carbon tetrachloride (CCl₄), BMSCs were administered for 4 weeks, and histopathological analysis and liver function tests were performed. T6 hepatic stellate cells (HSC-T6 cells) were stimulated by TGF-β1, and the activation and proliferation of cells were analyzed by CCK-8 assays, flow cytometry, real-time PCR, western blotting and enzyme-linked immunosorbent assay (ELISA). Results: Our data demonstrated that BMSCs effectively reduced the accumulation of collagen, enhanced liver functionality and ameliorated liver fibrosis in vivo. BMSCs increased the sub-G1 population in HSC-T6 cells. In addition, coculture with BMSCs reduced the expression of α-SMA, collagen I, cyclin-D1, and c-Myc in HSC-T6 cells and activated the phosphorylation of GSK3β. The GSK3β inhibitor SB216763 reversed the effect of BMSCs. The Wnt/β-catenin signalling pathway was involved in BMSC-mediated inhibition of HSC-T6 cell activation. Conclusions: Our data suggested that BMSCs exerted antifibrotic effects by activating the expression of GSK3β and inhibiting the Wnt3a/β-catenin signalling pathway.