Introduction: Studies have demonstrated that mesenchymal stromal cells (MSCs) could reverse acute and chronic kidney injury by a paracrine or endocrine mechanism, and microvesicles (MVs) have been regarded as a crucial means of intercellular communication. In the current study, we focused on the therapeutic effects of human Wharton-Jelly MSCs derived microvesicles (hWJMSC-MVs) in renal ischemia/reperfusion injury and its potential mechanisms. Methods: MVs isolated from conditioned medium were injected intravenously in rats immediately after ischemia of the left kidney for 60 minutes. The animals were sacrificed at 24 hours, 48 hours and 2 weeks after reperfusion. The infiltration of inflammatory cells was identified by the immunostaining of CD68+ cells. ELISA was employed to determine the inflammatory factors in the kidney and serum von Willebrand Factor (VWF). Tubular cell proliferation and apoptosis were identified by immunostaining. Renal fibrosis was assessed by Masson’s tri-chrome straining and alpha-smooth muscle actin (α-SMA) staining. The CX3CL1 expression in the kidney was measured by immunostaining and Western blot, respectively. In vitro, human umbilical vein endothelial cells were treated with or without MVs for 24 or 48 hours under hypoxia injury to test the CX3CL1 by immunostaining and Western blot. Results: After administration of hWJMSC-MVs in acute kidney injury (AKI) rats, renal cell apoptosis was mitigated and proliferation was enhanced, inflammation was also alleviated in the first 48 hours. MVs also could suppress the expression of CX3CL1 and decrease the number of CD68+ macrophages in the kidney. In the late period, improvement of renal function and abrogation of renal fibrosis were observed. In vitro, MVs could down-regulate the expression of CX3CL1 in human umbilical vein endothelial cells under hypoxia injury at 24 or 48 hours. Conclusions: A single administration of MVs immediately after ischemic AKI could ameliorate renal injury in both the acute and chronic stage, and the anti-inflammatory property of MVs through suppression of CX3CL1 may be a potential mechanism. This establishes a substantial foundation for future research and treatment.

Kaempferol is a well-known natural flavonol reported to be a potential treatment for multiple cancers. In this study, we demonstrated that cell growth of androgen-sensitive LNCaP cells could be inhibited 33% by 5 μM kaempferol, around 60% by 10 μM kaempferol, and almost 100% by 15 μM kaempferol. Also, kaempferol showed relatively limited effect on PC-3 cells and nonmalignant RWPE-1 cells. In the presence of DHT, the IC₅₀ for kaempferol was 28.8±1.5μM in LNCaP cells, 58.3±3.5μM in PC-3 cells, and 69.1±1.2μM in RWPE-1 cells, respectively. Kaempferol promotes apoptosis of LNCaP cells in a dose-dependent manner in the presence of dihydrotestosterone (DHT). Then, luciferase assay data showed that kaempferol could inhibit the activation of androgen receptors induced by DHT significantly. The downstream targets of androgen receptors, such as PSA, TMPRSS2, and TMEPA1, were found decreased in the presence of kaempferol in qPCR data. It was then confirmed that the protein level of PSA was decreased. Kaempferol inhibits AR protein expression and nuclear accumulation. Kaempferol suppressed vasculogenic mimicry of PC-3 cells in an in vitro study. In conclusion, kaempferol is a promising therapeutic candidate for treatment of prostate cancer, where the androgen signaling pathway as well as vasculogenic mimicry are involved.

Rationale: In urethral tissue engineering, the currently available reconstructive procedures are insufficient due to a lack of appropriate scaffolds that would support the needs of various cell types. To address this problem, we developed a bilayer scaffold comprising a microporous network of silk fibroin (SF) and a nanoporous bacterial cellulose (BC) scaffold and evaluated its feasibility and potential for long-segment urethral regeneration in a dog model.

The objective of this study was to investigate the feasibility of bladder acellular matrix grafts (BAMGs) seeded with adipose-derived stem cells (ASCs) followed by intraperitoneal incubation for bladder reconstruction in a rat model of bladder augmentation, and to explore the underlying mechanism. Autologous CM-DiI-labeled ASC-seeded (experimental group) and unseeded (control group) BAMGs were incubated in the peritoneum of male rats for 2 weeks and then harvested for bladder augmentation. Histological analysis of the incubated BAMGs revealed numerous cells growing in homogeneous collagen bundles in both groups. In the control BAMGs, these cells were mesenchyme derived, while in the ASC-seeded BAMGs, myofibroblasts and mesothelial cells were found inside and on the surface of the scaffold, respectively. Immunofluorescence analysis demonstrated that some of the myofibroblasts were transdifferentiated from the ASCs after 2 weeks of intraperitoneal incubation. The greater bladder capacity was found in the experimental group than the control group both 4 and 14 weeks postoperatively. Histological analysis revealed that the entire urothelium regenerated well both in the experimental group and the control group without significant difference 4 weeks and 14 weeks postoperatively. From the quantitative data of immunohistochemical and immunofluorescence staining, the smooth muscle cells (SMCs) regenerated significantly better in the experimental group than the control group both 4 weeks and 14 weeks postoperatively. Also significantly more nerve cells were found in the experimental group 14 weeks postoperatively. At 4 weeks postoperatively, the immunofluorescence double staining revealed that some SMCs in the BAMG were transdifferentiated from the implanted ASCs, but no CM-DiI labeling of ASCs was detected 14 weeks postoperatively. Taken together, our results demonstrate that ASC-seeded and peritoneally incubated BAMGs promote not only the morphological regeneration of the bladder smooth muscle and nerve, but also the bladder capacity, which indicates their potential for bladder regeneration.