Systems level approach reveals the correlation of endoderm differentiation of mouse embryonic stem cells with specific microstructural cues of fibrin gels

Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications.     

Multiwall carbon nanotubes as MRI contrast agents for tracking stem cells

In this study we investigate the potential of multiwall carbon nanotubes (MWCNTs) with low metal impurities (2.57% iron) as magnetic resonance imaging (MRI) contrast agents. Taking into account probable aggregation at high MWCNTs concentration analysis shows that the r(2) relaxivity of MWCNTs in 1% agarose gels at 19?°C is 564 ± 41 s(-1) mM(-1); this is attributed to both the presence of iron oxide impurities and also to the carbon MWCNT structure itself. Stem cells were labelled with MWCNTs to demonstrate the effectiveness of MWCNTs as MRI contrast agents for cellular MRI. The MWCNTs did not impair cell viability or proliferation. These results suggest that the MRI contrast agent properties of the MWCNTs could be used in vivo for stem cell tracking/imaging and during MWCNT-mediated targeted electro-chemotherapy of tumours.     

Emulsion electrospun nanofibers as substrates for cardiomyogenic differentiation of mesenchymal stem cells

The potential of cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs) on emulsion electrospun scaffold containing poly(l-lactic acid)-co-poly-(ε-caprolactone), gelatin and vascular endothelial growth factor (PLCL/GV) was investigated in this study. The characterizations of the scaffold were carried out using scanning electron microscope (SEM), transmission electron microscope, water contact angle and porometer. The proliferation of hMSCs showed that 73.4 % higher cell proliferation on PLCL/GV scaffolds than that on PLCL scaffold after 20 days of cell culture. Results of 5-chloromethylfluorescein diacetate staining and SEM morphology analysis indicated that hMSCs differentiated on PLCL/GV scaffolds showed irregular morphology of cardiomyocyte phenotype compared to the typical long and thin hMSC phenotype. Immunostaining results showed the expression of alpha actinin and myosin heavy chain. Our studies identified emulsion electrospinning as a method for fabrication of core–shell fibers suitable for the differentiation of stem cells to cardiac cells, with potential application in cardiac regeneration.     

Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study

The objectives of this study were to: (1) develop an injectable and biodegradable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the stem cell viability, and osteogenic differentiation of the stem cells in vitro. Stem cells were encapsulated using alginate hydrogel. The stem cell viability, proliferation and differentiation to adipogenic and osteogenic tissues were studied. To investigate the expression of both adipogenesis and ontogenesis related genes, the RNA was extracted and RT-PCR was performed. The degradation behavior of hydrogel based on oxidized sodium alginate with different degrees of oxidation was studied in PBS at 37?°C as a function of time by monitoring the changes in weight loss. The swelling kinetics of alginate hydrogel was also investigated. The results showed that alginate is a promising candidate as a non-toxic scaffold for PDLSCs and GMSCs. It also has the ability to direct the differentiation of these stem cells to osteogenic and adipogenic tissues as compared to the control group in vitro. The encapsulated stem cells remained viable in vitro and both osteo-differentiated and adipo-differentiated after 4?weeks of culturing in the induction media. It was found that the degradation profile and swelling kinetics of alginate hydrogel strongly depends on the degree of oxidation showing its tunable chemistry and degradation rate. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in the alginate microspheres provides a promising strategy for bone tissue engineering.     

SPION nanoparticles as an efficient probe and carrier of DNA to umbilical cord blood-derived mesenchymal stem cells

Superparamagnetic iron oxide nanoparticles (SPION) were used to transfer gene into umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in this study. This novel transfection method using SPION is safe and effective to UCB-MSCs, and would be a tool for genetic optimization with a significant potential for cell tracing.     

Citations versus journal impact factor as proxy of quality: could the latter ever be preferable?

In recent years bibliometricians have paid increasing attention to research evaluation methodological problems, among these being the choice of the most appropriate indicators for evaluating quality of scientific publications, and thus for evaluating the work of single scientists, research groups and entire organizations. Much literature has been devoted to analyzing the robustness of various indicators, and many works warn against the risks of using easily available and relatively simple proxies, such as journal impact factor. The present work continues this line of research, examining whether it is valid that the use of the impact factor should always be avoided in favour of citations, or whether the use of impact factor could be acceptable, even preferable, in certain circumstances. The evaluation was conducted by observing all scientific publications in the hard sciences by Italian universities, for the period 2004–2007. Performance sensitivity analyses were conducted with changing indicators of quality and years of observation.     

First standard released to regulate the study and use of stem cells

正China’s first general standard for stem cells officially released on November 22,2017 is expected to lay a foundation for regulating the application of stem cells technology.Stem cells are a group of self-renewal cells that can differentiate into specialized cells.They are now used for the treatment of many diseases.Despite a series of documents for regulating basic research and achievement transformation of stem cells,the clinical application and industrialization still face great challenges due to diverse     

Effects of chondrogenic and osteogenic regulatory factors on composite constructs grown using human mesenchymal stem cells, silk scaffolds and bioreactors.

Human mesenchymal stem cells (hMSCs) isolated from bone marrow aspirates were cultured on silk scaffolds in rotating bioreactors for three weeks with either chondrogenic or osteogenic medium supplements to engineer cartilage- or bone-like tissue constructs. Osteochondral composites formed from these cartilage and bone constructs were cultured for an additional three weeks in culture medium that was supplemented with chondrogenic factors, supplemented with osteogenic factors or unsupplemented. Progression of cartilage and bone formation and the integration between the two regions were assessed by medical imaging (magnetic resonance imaging and micro-computerized tomography imaging), and by biochemical, histological and mechanical assays. During composite culture (three to six weeks), bone-like tissue formation progressed in all three media to a markedly larger extent than cartilage-like tissue formation. The integration of the constructs was most enhanced in composites cultured in chondrogenic medium. The results suggest that tissue composites with well-mineralized regions and substantially less developed cartilage regions can be generated in vitro by culturing hMSCs on silk scaffolds in bioreactors, that hMSCs have markedly higher capacity for producing engineered bone than engineered cartilage, and that chondrogenic factors play major roles at early stages of bone formation by hMSCs and in the integration of the two tissue constructs into a tissue composite.     

肿瘤干细胞活体示踪的分子影像学研究进展

肿瘤干细胞(Cancer Stem Cell,CSCs)是肿瘤细胞中具有自我更新和多向分化能力的细胞,与肿瘤的发生、增殖、转移和耐药等生物学行为关系密切,CSCs的活体示踪对于实时监测CSCs在体内的生物学行为具有重要意义。目前常见CSCs活体示踪的分子影像学方法包括:超声成像、核磁共振成像(Magnetic Resonance Imaging,MRI)、光学成像、核医学成像(Positron Emission Tomography-Computed Tomography,PET-CT)、光声成像、多模态成像。这些成像方法的发展对于CSCs的研究具有重大意义,对于CSCs的研究有助于临床诊断及治疗,有利于诊疗一体化进程的发展。文章就CSCs活体示踪的分子影像学研究进展进行了综述。     

Co-word analysis of the trends in stem cells field based on subject heading weighting

In this paper, co-word analysis is used to analyze the evolvement in stem cell field. Articles in the stem cell journals are downloaded from PubMed for analysis. Terms selection is one of the most important steps in co-word analysis, so the useless and the general subject headings are removed firstly, and then the major subject headings and minor subject headings are weighted respectively. Then, improved information entropy is exploited to select the subject headings with the experts consulting. Hierarchical cluster analysis is used to cluster the subject headings and the strategic diagram is formed to analyze the evolutionary trends in the stem cell field.     

Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement.     

A spatially and chemically defined platform for the uniform growth of human pluripotent stem cells

We report the design of a chemically defined platform engineered for the culture of human pluripotent stem cells (hPSCs) that supports the long-term maintenance of self-renewing hPSC populations in a more uniform manner than standard culture systems. Microcontact printing (μCP) of alkanethiol self-assembled monolayers (SAMs) was used to spatially direct hPSC adherence. This technique not only establishes control over hPSC colony size and shape but also preserves genetic stability and provides unprecedented uniformity in the pluripotency of hPSC populations that is quantitatively assessed in the present study.     

Carbon nanotube rope with electrical stimulation promotes the differentiation and maturity of neural stem cells

In recent years, the utilization of nanomaterials such as carbon nanotubes (CNTs) in the field of neuroscience has forever changed the approach to nerve-related research. The array of novel properties CNTs possess allows them to interact with neurons at the nanodimensional scale. In this study, a CNT rope substrate is developed to allow the electrical stimulation of neural stem cells (NSCs) in culture medium and the in situ observation of the response of these stem cells after stimulation. CNTs are synthesized by chemical vapor deposition and prepared into a ropelike structure with a diameter of 1 mm and length of 1.5 cm. NSCs are differentiated on the CNT rope substrate while the direction of neurite outgrowth, phenotype, and maturity of the NSCs are analyzed. Fluorescence and scanning electron microscopy demonstrate that neurite extension favors the direction of the spiral topography on the CNT rope. NSCs plated on CNT ropes are boosted towards differentiated neurons in the early culture stage when compared to conventional tissue culture plates via the analysis of neuronal gene and protein expressions by quantitative polymerase chain reaction and immunostaining, respectively. Furthermore, a set of electrical stimulation parameters (5 mV, 0.5 mA, 25 ms intermittent stimulation) promotes neuronal maturity while also increasing the speed of neurite outgrowth. These results indicate that an electroconductive CNT rope substrate along with electrical stimulation may have a synergistic effect on promoting neurite elongation and boosting effects on the differentiation of NSCs into mature neuronal cells for therapeutic application in neural regeneration.     

Characterization of a PLGA sandwiched cell/fibrin tubular construct and induction of the adipose derived stem cells into smooth muscle cells

A poly(dl-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor β1 (TGFβ1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing.