Nomogram based on the O-RADS for predicting the malignancy risk of adnexal masses with complex ultrasound morphology.

OBJECTIVE: The accurate preoperative differentiation of benign and malignant adnexal masses, especially those with complex ultrasound morphology, remains a great challenge for junior sonographers. The purpose of this study was to develop and validate a nomogram based on the Ovarian-Adnexal Reporting and Data System (O-RADS) for predicting the malignancy risk of adnexal masses with complex ultrasound morphology. METHODS: A total of 243 patients with data on adnexal masses with complex ultrasound morphology from January 2019 to December 2020 were selected to establish the training cohort, while 106 patients with data from January 2021 to December 2021 served as the validation cohort. Univariate and multivariate analyses were used to determine independent risk factors for malignant tumors in the training cohort. Subsequently, a predictive nomogram model was developed and validated in the validation cohort. The calibration, discrimination, and clinical net benefit of the nomogram model were assessed separately by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Finally, we compared this model to the O-RADS. RESULTS: The O-RADS category, an elevated CA125 level, acoustic shadowing and a papillary projection with color Doppler flow were the independent predictors and were incorporated into the nomogram model. The area under the ROC curve (AUC) of the nomogram model was 0.958 (95% CI, 0.932-0.984) in the training cohort. The specificity and sensitivity were 0.939 and 0.893, respectively. This nomogram also showed good discrimination in the validation cohort (AUC = 0.940, 95% CI, 0.899-0.981), with a sensitivity of 0.915 and specificity of 0.797. In addition, the nomogram model showed good calibration efficiency in both the training and validation cohorts. DCA indicated that the nomogram was clinically useful. Furthermore, the nomogram model had higher AUC and net benefit than the O-RADS. CONCLUSION: The nomogram based on the O-RADS showed a good predictive ability for the malignancy risk of adnexal masses with complex ultrasound morphology and could provide help for junior sonographers.

Towards Standardized Stem Cell Therapy in Type 2 Diabetes Mellitus: A Systematic Review.

OBJECTIVE: To compile and analyze the published studies on cell therapy for type 2 diabetes mellitus (T2DM) to obtain a better insight into management of T2DM that involved stem cell therapy. METHODS: We searched all published studies in Pubmed/Medline, and Cochrane library, using keywords: 'stem cell' AND 'therapy' AND 'diabetes type 2'. Inclusion criteria: original articles on the use of stem cells in humans with T2DM. Exclusion criteria: articles in the non-English literature, studies on T2DM complications that did not assess both adverse events and any of the common diabetes study outcomes. Data collection: type of study, number of cases, and all data that were related to outcome and adverse events. Data were analyzed descriptively to conclude the possible cause of adverse reactions, and which protocols gave a satisfactory outcome. RESULTS: We collected 25 original articles, out of which 17 studies did not have controls and were classified as case reports, while there were 8 studies that were controlled clinical trials. Most studies used autologous bone marrow mononuclear cells (BM-MNCs) or autologous or allogeneic mesenchymal stem cells (MSCs) from various sources. Adverse events were mild and mostly intervention related. Efficacy of autologous BM-MNCs that were given via interventional route was comparable to Wharton jelly or umbilical cord MSCs that were given via intravenous (IV), Intra muscular (IM), or subcutaneous (SC) route. CONCLUSION: Further controlled studies that compare BM-MNCs to BM-MSCs or WJ-MSCs or UCSCs are recommended to prove their comparable efficacy. In addition, studies that compare various routes of administration (IV, IM or SC) versus the more invasive interventional routes are needed.

Substrate topography determines the fate of chondrogenesis from human mesenchymal stem cells resulting in specific cartilage phenotype formation.

To reproduce a complex and functional tissue, it is crucial to provide a biomimetic cellular microenvironment that not only incorporates biochemical cues, but also physical features including the nano-topographical patterning, for cell/matrix interaction. We developed spatially-controlled nano-topography in the form of nano-pillar, nano-hole and nano-grill on polycaprolactone surface via thermal nanoimprinting. The effects of chondroitin sulfate-coated nano-topographies on cell characteristics and chondrogenic differentiation of human mesenchymal stem cell (MSC) were investigated. Our results show that various nano-topographical patterns triggered changes in MSC morphology and cytoskeletal structure, affecting cell aggregation and differentiation. Compared to non-patterned surface, nano-pillar and nano-hole topography enhanced MSC chondrogenesis and facilitated hyaline cartilage formation. MSCs experienced delayed chondrogenesis on nano-grill topography and were induced to fibro/superficial zone cartilage formation. This study demonstrates the sensitivity of MSC differentiation to surface nano-topography and highlights the importance of incorporating topographical design in scaffolds for cartilage tissue engineering. From the clinical editor: These authors have developed spatially-controlled nano-topography in the form of nano-pillar, nano-hole and nano-grill on polycaprolactone surface via thermal nanoimprinting, and the effects of chondroitin sulfate-coated nano-topographies on cell characteristics and chondrogenic differentiation of human mesenchymal stem cells (MSC) were investigated. It has been concluded that MSC differentiation is sensitive to surface nano-topography, and certain nano-imprinted surfaces are more useful than others for cartilage tissue engineering.

Effects of ectopic Nanog and Oct4 overexpression on mesenchymal stem cells.

Mesenchymal stem cells (MSCs) represent a source of pluripotent cells that are already in various phases of clinical application. However, the use of MSCs in tissue engineering has been hampered largely due to their limitations, including low proliferation, finite life span, and gradual loss of their stem cell properties during ex vivo expansion. Nanog and Oct4 are key transcription factors essential to the pluripotent and self-renewing phenotypes of undifferentiated embryonic stem cells (ESCs). To determine whether Nanog and Oct4 improve human bone marrow-MSC quality, we therefore established stable Nanog and Oct4 overexpressing MSCs using a lentiviral system and showed that this promoted cell proliferation and enhanced colony formation of MSCs. In differentiating MSCs, Nanog, and Oct4, overexpression had converse effects on adipogenesis of MSCs and Nanog overexpression slowed down adipogenesis, whereas Oct4 overexpression improved adipogenesis. Nanog and Oct4 overexpression both improved chondrogenesis. Microarray data showed many differences in transcriptional targets in undifferentiated MSCs overexpressing Nanog and Oct4. These results provide insight into the improvement of the stemness of MSCs by genetic modification with stemness-related genes.

Cartilaginous ECM component-modification of the micro-bead culture system for chondrogenic differentiation of mesenchymal stem cells.

In this study a 3-D alginate microbead platform was coated with cartilaginous extracellular matrix (ECM) components to emulate chondrogenic microenvironment in vivo for the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). BMSCs were seeded onto the microbead surface and the effect of the modified microbead on BMSC adhesion, proliferation and chondrogenic differentiation was studied, and compared to chondrogenesis in conventional pellet culture. Our results indicated that microbead system promoted BMSC proliferation and protein deposition resulting in the formation of bigger aggregates compared to conventional pellet culture. Analysis of the aggregates indicated that chondroitin sulfate (CS)- and Col2-coated microbeads enhanced the chondrogenic differentiation of hBMSCs, with increasing formation of glycosaminoglycan (GAG) and collagen II deposition in histology, immunohistochemistry and real time PCR analysis. In addition, Col2-coated microbeads resulted in hypertrophic maturation of the differentiated chondrocytes, similar to conventional pellet culture, while CS-coated microbeads were able to retain the pre-hypertrophy state of the differentiated cells. Our result suggested that provision of suitable cartilaginous microenvironment in a 3-D system can promote the chondrogenic differentiation of BMSC and influence the phenotype of resulting chondrocytes. Our microbead system provides an easy method of processing a 3-D alginate system that allows the possibility of scaling up chondrogenic pellet production for clinical application, while the modifiable microbeads also provide an adjustable 3-D platform for the study of co-interaction of ECM and differentiation factors during the stem cell differentiation.

Optimization of 3-D hepatocyte culture by controlling the physical and chemical properties of the extra-cellular matrices.

Hepatocytes are anchorage-dependent cells sensitive to microenvironment; the control of the physicochemical properties of the extra-cellular matrices may be useful to the maintenance of hepatocyte functions in vitro for various applications. In a microcapsule-based 3-D hepatocyte culture microenvironment, we could control the physical properties of the collagen nano-fibres by fine-tuning the complex-coacervation reaction between methylated collagen and terpolymer of hydroxylethyl methacrylate-methyl methacrylate-methylacrylic acid. The physical properties of the nano-fibres were quantitatively characterized using back-scattering confocal microscopy to help optimize the physical support for hepatocyte functions. We further enhanced the chemical properties of the collagen nano-fibres by incorporating galactose onto collagen, which can specifically interact with the asialoglycoprotein receptor on hepatocytes. By correlating a range of collagen nano-fibres of different physicochemical properties with hepatocyte functions, we have identified a specific combination of methylated and galactosylated collagen nano-fibres optimal for maintaining hepatocyte functions in vitro. A model of how the physical and chemical supports interplay to maintain hepatocyte functions is discussed.