Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells.

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined. AIM: To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI. METHODS: Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs). RESULTS: Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. CONCLUSION: Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

An miRNA-mRNA integrative analysis in human placentas and mice: role of the Smad2/miR-155-5p axis in the development of fetal growth restriction.

Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology. Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice. Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = -0.471, p < 1.0 E - 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/- heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal. Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.

[Preparation of multifunctional nanoparticles targeting tongue cancer and in vitro study].

OBJECTIVE: This study aims to prepare docetaxel (DOC)-loaded multifunctional nanoparticles containing indocyanine green (ICG) and perfluorohexane (PFH) as targeted drug delivery system, which is supplemented with stromal cellderived factor-1 (SDF-1), and characterize their properties. METHODS: Multifunctional nanoparticles were prepared by using the double emulsion method. SDF-1 was covalently conjugated to the surface of the nanoparticles through thioether bonding. Their particle size, distribution, and surface potential were determined with the Malvern measuring instrument. The conjugation of SDF-1 was evaluated by confocal laser scanning microscope. Encapsulation efficiency (ELC), drug loading capacity (DLC), and release regularity of the nanoparticles were determined by high-performance liquid chromatography (HPLC). In vitro photothermal property was recorded by a thermal imager. The in vitro imaging capacity was observed by a photoacoustic instrument and an ultrasonic diagnostic apparatus. Targeting capability was assessed by flow cytometry. The cell activity on SCC-15 cells was checked by CCK-8 method. RESULTS: The targeted multifunctional nanoparticles showed regularly sphericity. The diameter was (502.88±17.92) nm. The zeta potential was (-11.5±3.15) mV. ELC was 54.12%±1.74%. DLC was 1.08 mg·mL-1. In vitro drug release was initially fast and subsequently slow. The photothermal characteristics were related to the concentration; the higher the concentration, the higher the temperature. Nanoparticles could detect significant photoacoustic and ultrasound signals. The in vitro targeting rate was 89.99%. No significant differences of cell viability in the SINPs groups were observed at each concentration (P>0.05). The inhibition effect of DOC-SINPs was stronger than that of SINPs whether or not in the presence of laser irradiation among the groups of 150 and 200 µg·mL-1 (P<
0.05). CONCLUSIONS: Multifunctional nanoparticles for diagnosis and treatment were successfully prepared and displayed dualmode ultrasound/photoacoustic imaging and antitumor effects of chemotherapy and photothermal therapy.