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Skin fibroblasts obtained from a 5-year-old girl with genetically proven (two heterozygous mutations in ARSB gene) and clinically manifested mucopolysaccharidosis type VI were successfully transformed into induced pluripotent stem cells by using Sendai virus-based reprogramming vectors including the four Yamanaka factors namely SOX2, OCT3/4, KLF4, and c-MYC. These iPSCs expressed pluripotency markers, had a normal karyotype and the potential to differentiate into three germ layers in spontaneous differentiation assay. The line may be used for cell differentiation and pharmacological investigations, and also may provide a model for development of a personalized treatment including drug screening and genome editing.

Urine cells obtained from a 14-year-old man with genetically proven (ACVR1: c.6176G > A) and clinically manifested fibrodysplasia ossificans progressiva were successfully transformed into induced pluripotent stem cells by using Sendai virus-based reprogramming vectors including the four Yamanaka factors such as OCT3/4, SOX2, KLF4, and c-MYC. These iPSCs expressed pluripotency markers, exhibited the potential to differentiate into three germ layers in spontaneous differentiation assay and had a normal karyotype. The iPSC line may provide a model for development of a personalized treatment including genome editing and drug screening, may be used for disease modelling, cell differentiation and pharmacological investigations..

The development of tissue fibrosis is a complex process involving the interaction of multiple cell types, which makes the search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered the key cell type that mediated the development of fibrosis and thus was the main target for therapy. However, current strategies aimed at inhibiting myofibroblast function or eliminating them fail to demonstrate sufficient effectiveness in clinical practice. Therefore, today, there is an unmet need to search for more reliable cellular targets to contribute to fibrosis resolution or the inhibition of its progression. Activated stromal cells, capable of active proliferation and invasive growth into healthy tissue, appear to be such a target population due to their more accessible localization in the tissue and their high susceptibility to various regulatory signals. This subpopulation is marked by fibroblast activation protein alpha (FAPα). For a long time, FAPα was considered exclusively a marker of cancer-associated fibroblasts. However, accumulating data are emerging on the diverse functions of FAPα, which suggests that this protein is not only a marker but also plays an important role in fibrosis development and progression. This review aims to summarize the current data on the expression, regulation, and function of FAPα regarding fibrosis development and identify promising advances in the area.

Multipotent mesenchymal stromal cells (MSCs) maintain cellular homeostasis and regulate tissue renewal and repair both by differentiating into mesodermal lineage, e.g., adipocytes, or managing the functions of differentiated cells. Insulin is a key physiological inducer of MSC differentiation into adipocytes, and disturbances in MSC insulin sensitivity could negatively affect adipose tissue renewal. During aging, regulation and renewal of adipose tissue cells may be disrupted due to the altered insulin signaling and differentiation potential of senescent MSCs, promoting the development of serious metabolic diseases, including metabolic syndrome and obesity. However, the potential mechanisms mediating the dysfunction of adipose-derived senescent MSC remains unclear. We explored whether aging could affect the adipogenic potential of human adipose tissue-derived MSCs regulated by insulin. Age-associated senescent MSCs (isolated from donors older than 65 years) and MSCs in replicative senescence (long-term culture) were treated by insulin to induce adipogenic differentiation, and the efficiency of the process was compared to MSCs from young donors. Insulin-dependent signaling pathways were explored in these cells. We also analyzed the involvement of extracellular vesicles secreted by MSCs (MSC-EVs) into the regulation of adipogenic differentiation and insulin signaling of control and senescent cells. Also the microRNA profiles of MSC-EVs from aged and young donors were compared using targeted PCR arrays. Both replicatively and chronologically senescent MSCs showed a noticeably decreased adipogenic potential. This was associated with insulin resistance of MSCs from aged donors caused by the increase in the basal level of activation of crucial insulin-dependent intracellular effectors ERK1/2 and Akt. To assess the impact of the paracrine cross-talk of MSCs, we analyzed microRNAs profile differences in MSC-EVs and revealed that senescent MSCs produced EVs with increased content of miRNAs targeting components of insulin-dependent signaling cascade PTEN, MAPK1, GAREM1 and some other targets. We also confirmed these data by differentiation of control MSCs in the presence of EVs from senescent cells and vice versa. Thus, aging attenuated the adipogenic potential of MSCs due to autocrine or paracrine-dependent induction of insulin resistance associated with the specific changes in MSC-EV cargo.

Induced pluripotent stem cells (iPSCs) was successfully generated from skin fibroblast obtained from patient with cystic fibrosis by using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit, which contain three vectors preparation: polycistronic Klf4–Oct3/4–Sox2, cMyc, and Klf4. Created iPSC lines showed a normal karyotype, expressed pluripotency markers and demonstrated the potential to differentiate into three germ layers in spontaneous differentiation assay.

Skin fibroblasts obtained from a 20-year-old woman with clinically manifested and genetically proven (F508del/CFTRdele2.3) cystic fibrosis were successfully transformed into induced pluripotent stem cells (iPSCs) by using Sendai virus-based reprogramming vectors including the four Yamanaka factors, OCT3/4, SOX2, KLF4, and c-MYC. The iPSCs showed a normal karyotype, expressed pluripotency markers and exhibited the potential to differentiate into three germ layers in spontaneous differentiation assay. This iPSC line may be used for development of a personalized treatment including genome editing, disease modelling, cell differentiation and organoid formation, pharmacological investigations and drug screening.

Mesenchymal stromal cells (MSCs) are the key regulators of tissue homeostasis and repair after damage. Accumulating evidence indicates the dual contribution of MSCs into the development of fibrosis induced by chronic injury: these cells can suppress the fibrotic process due to paracrine activity, but their promoting role in fibrosis by differentiating into myofibroblasts has also been demonstrated. Many model systems reproducing fibrosis have shown the ability of peroxisome proliferator-activated receptor (PPAR) agonists to reverse myofibroblast differentiation. Thus, the differentiation of multipotent cells into myofibroblasts and adipocytes can be considered as processes that require the activation of opposite patterns of gene expression. To test this hypothesis, we analyzed single cell RNA-Seq transcriptome of human adipose tissue MSCs after stimulation of the myofibroblast or adipogenic differentiation and revealed several genes that changed their expression in a reciprocal manner upon these conditions. We validated the expression of selected genes by RT-PCR, and evaluated the upregulation of several relevant proteins using immunocytochemistry, refining the results obtained by RNA-Seq analysis. We have shown, for the first time, the expression of neurotrimin (NTM), previously studied mainly in the nervous tissue, in human adipose tissue MSCs, and demonstrated its increased gene expression and clustering of membrane receptors upon the stimulation of myofibroblast differentiation. We also showed an increased level of CHD3 (Chromodomain-Helicase-DNA-binding protein 3) in MSCs under profibrotic conditions, while retinol dehydrogenase-10 (RDH10) was detected only in MSCs after adipogenic induction, which contradicted the data of transcriptomic analysis and again highlights the need to validate the data obtained by omics methods. Our findings suggest the further analysis of the potential contribution of neurotrimin and CHD3 in the regulation of myofibroblast differentiation and the development of fibrosis.

Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells. Despite the fact that a sympathetic outflow increases in individuals with obesity, as a rule, there is a cohort of patients with obesity who do not develop hypertension. In this study, we investigated how adrenoceptors’ expression and functioning in adipose tissue are affected by obesity-driven hypertension. Here, we demonstrated that α1A is a predominant isoform of α1-adrenoceptors expressed in the adipose tissue of patients with obesity, specifically by multipotent mesenchymal stromal cells (MSCs). These cells respond to prolonged exposure to noradrenaline in the model of sympathetic overdrive through the elevation of α1A-adrenoceptor expression and signaling. The extent of MSCs’ response to noradrenaline correlates with a patient’s arterial hypertension. scRNAseq analysis revealed that in the model of sympathetic overdrive, the subpopulation of MSCs with contractile phenotype expanded significantly. Elevated α1A-adrenoceptor expression is triggered specifically by beta3-adrenoceptors. These data define a novel pathophysiological mechanism of obesity-driven hypertension by which noradrenaline targets MSCs to increase microvessel constrictor responsivity.

Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades, the pool of adult mesenchymal stem/stromal cells (MSCs) remains a promising source of stem and progenitor cells. Their isolation is more feasible than most other stem cells from human donors, yet they have a fair share of drawbacks. They include significant variability between donors, loss of potency, and transformation during long-term culture, which may impact the efficacy and reproducibility of research. One possible solution is a derivation of immortalized MSCs lines which receive a broader use in many medical and biological studies. In the present work, we demonstrated that in the most widely spread commercially available hTERT-immortalized MSCs cell line ASC52telo, sensitivity to hormonal stimuli was reduced, affecting their differentiation efficacy. Furthermore, we found that immortalized MSCs have impaired insulin-dependent and cAMP-dependent signaling, which impairs their adipogenic, but not osteogenic or chondrogenic, potential under experimental conditions. Our findings indicate that hTERT-immortalized MSCs may present a suboptimal choice for studies involving modeling or investigation of hormonal sensitivity.

Abstract Background Injury of stem cell niches may disturb tissue homeostasis and regeneration coordinated by specific niche components. Yet, the mechanisms of stem cell niche restoration remain poorly understood. Herein, we examined the role of mesenchymal stromal cells (MSCs) as pivotal regulators of stem cell niche recovery focusing on the effects of their secretome. Methods The spermatogonial stem cell (SSC) niche was selected as a model. SSC niches were injured by inducing abdominal cryptorchidism in rats. Briefly, testes of anesthetized rats were elevated into the abdominal cavity through the inguinal canal for 14 days. After descent of testes, MSC or MSC secretome treatment was applied to the animals by local subtunical injections. Results Local administration of MSC or MSC secretome was sufficient to recover spermatogenesis and production of functional germ cells. The effects of MSC and their secreted components were comparable, leading to restoration of Sertoli cell pools and recovery of Leydig cell secretory functions. Conclusion Our data suggest that MSCs mimic the functions of lost supportive cells within the stem cell niche, transiently providing paracrine stimuli for target cells and triggering tissue regenerative processes after damage.

Besides certain exceptions, healing of most tissues in the human body occurs via formation of scar tissue, rather than restoration of lost structures. After extensive acute injuries, this phenomenon substantially limits the possibility of lost function recovery and, in case of chronic injury, it leads to pathological remodeling of organs affected. Managing outcomes of damaged tissue repair is one of the main objectives of regenerative medicine. The first priority for reaching it is comparative investigation of mechanisms responsible for complete restoration of damaged tissues and mechanisms of scarring. However, human body tissues that undergo complete scar-free healing are scarce. The endometrium is a unique mucous membrane in the human body that heals without scarring after various injuries, as well as during each menstrual cycle (i.e., up to 400 times during a woman’s life). We hypothesized that absence of scarring during endometrial healing may be associated with tissue-specific features of its stromal cells (SCs) or their microenvironment, since SCs transform into myofibroblasts—the main effector link of scarring. We found that during healing of the endometrium, soluble factors are formed that inhibit the transition of SCs into myofibroblasts. Without influence of these factors, the SCs of the endometrium undergo transformation into myofibroblasts after transforming growth factor β1 (TGF-β1) treatment as well as the SCs from tissues that heal by scarring—skin or fat. However, unlike the latter, endometrial SCs organize extracellular matrix (ECM) in a specific way and are not prone to formation of bulky connective tissue structures. Thus, we may suggest that tissue-specific features of endometrial SCs along with effects of soluble factors secreted in utero during menstruation ensure scar-free healing of human endometrium.

Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.

This study proposes an original method for tree species classification by satellite remote sensing. The method uses multitemporal multispectral (Landsat OLI) and hyperspectral (Resurs-P) data acquired from determined vegetation periods. The method is based on an original database of spectral features taking into account seasonal variations of tree species spectra. Changes in the spectral signatures of forest classes are analyzed and new spectral–temporal features are created for the classification. Study sites are located in the Czech Republic and northwest (NW) Russia. The differences in spectral reflectance between tree species are shown as statistically significant in the sub-seasons of spring, first half of summer, and main autumn for both study sites. Most of the errors are related to the classification of deciduous species and misclassification of birch as pine (NW Russia site), pine as mixture of pine and spruce, and pine as mixture of spruce and beech (Czech site). Forest species are mapped with accuracy as high as 80% (NW Russia site) and 81% (Czech site). The classification using multitemporal multispectral data has a kappa coefficient 1.7 times higher than does that of classification using a single multispectral image and 1.3 times greater than that of the classification using single hyperspectral images. Potentially, classification accuracy can be improved by the method when applying multitemporal satellite hyperspectral data, such as in using new, near-future products EnMap and/or HyspIRI with high revisit time.

This manuscript considers the design of a slotted adaptive hydrostatic thrust bearing with a regulator of the lubricant output flow. A theoretical study of its static and dynamic characteristics was carried out. The aim of the study was to test the reliability of the hypothesis concerning the possibility of obtaining a stable-to-oscillation adaptive thrust bearing of negative compliance, avoiding the need for a complex system of external combined throttling by replacing it with a simple slotted throttle. Mathematical modeling of the thrust bearing movement was carried out. The possibility of reducing the compliance to negative values is shown, providing the bearing with an adaptive function, consisting of using the structure as a bearing and as an active deformation compensator of the elastic system of a metal-cutting machine in order to improve the quality of the metalwork. Analysis of load static characteristics showed that negative compliance is provided over a wide range of loads, which can be up to 75% or more of the range of permissible bearing loads. Based on the study of dynamic characteristics, it was concluded that with a targeted selection of parameters that have a major effect on the dynamics of the structure, the considered adaptive hydrostatic thrust bearing can attain a very high quality of dynamics. It is shown that the viscous damping of the lubricating film enclosed in the gaps and the damping of the material of the elastic ring of the regulator are important resources for ensuring the optimal dynamics of the thrust bearing.

The design is considered and theoretical research of operability of the active radial gas-static bearing with restrictors of output flow rate in the form of mobile rings with an elastic supports and the dampers working by Helmholtz acoustic resonator principle is done. The mathematical model of the bearing dynamics and method of calculating its degree of stability are developed. The device is steady against vibrations; it has smaller power consumption compared to the known devices with input regulators, a zero and negative compliance of a gas-lubricated film.

Stepped hydrostatic thrust bearings used in metal-cutting machines are characterized by high load capacity and damping, which ensure the stable operation of structures. However, in comparison with throttle thrust bearings, they have a high compliance. It is preferable that, in addition to the main bearing function, a modern hydrostatic bearing has the ability to provide low (including negative) compliance for the implementation of an adaptive function in order to actively compensate for the deformation of the machine resilient system, thereby increasing the accuracy of metalworking. This paper considers the design of a stepped hydrostatic thrust bearing, which, in order to reduce the compliance to negative values, features a technical improvement consisting of the use of an active displacement compensator on an elastic suspension. In this paper, the results of mathematical modeling and theoretical research of stationary and non-stationary modes of operation of the adaptive thrust bearing are presented. The possibility of a significant reduction in the static compliance of the structure, including the negative compliance values, is shown. It was found that negative compliance is provided in a wide range of loads, which can be up to 80% of the range of permissible bearing loads. The study of the dynamic characteristics showed that with a targeted selection of parameters that ensure optimal performance, the adaptive thrust bearing is able to operate stably in the entire range of permissible loads. It has been established that an adaptive stepped hydrostatic thrust bearing with a displacement compensator has a high stability margin, sufficient to ensure its operability when implementing the adaptive function.

Activation of multipotent mesenchymal stromal cells (MSCs) is a central part of tissue response to damage. Platelet-derived growth factor (PDGF-BB), which is abundantly released in the damaged area, potently stimulates the proliferation and migration of MSCs. Recent evidence indicates that tissue injury is associated with the accumulation of senescent cells, including ones of MSC origin. Therefore, we hypothesized that PDGF-BB induces MSC senescence. To evaluate mechanisms of early activation of MSCs by PDGF-BB, we performed transcriptome profiling of human MSCs isolated from adipose tissue after exposure to PDGF-BB for 12 and 24 h. We demonstrated that PDGF-BB induced the expression of several genes encoding the components of senescence-associated secretory phenotype (SASP) in MSCs such as plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR), and some matrix metalloproteases. However, further experimental validation of transcriptomic data clearly indicated that PDGF-BB exerted mitogenic and pro-migratory effects on MSCs, and augmented their pro-angiogenic activity, but did not significantly stimulate MSC senescence.

Due to their vanishingly low air friction, high wear resistance, and environmental friendliness, aerostatic bearings are used in machines, machine tools, and devices that require high accuracy of micro-movement and positioning. The characteristic disadvantages of aerostatic bearings are low load capacity, high compliance and an increased tendency for instability. In radial bearings, it is possible to use longitudinal microgrooves, which practically exclude circumferential air leakage, and contributes to a significant increase in load-bearing capacity. To reduce compliance to zero and negative values, inlet diaphragm and elastic airflow regulators are used. Active flow compensation is inextricably linked to the problem of ensuring the stability of bearings due to the presence of relatively large volumes of gas in the regulator, which have a destabilizing effect. This problem was solved by using an external combined throttling system. Bearings with input flow regulators have a number of disadvantages-they are very energy-intensive and have an insufficiently stable load capacity. A more promising way to reduce compliance is the use of displacement compensators for the movable element. Such bearings also allow for a decrease in compliance to zero and negative values, which makes it possible to use them not only as supports, but also as active deformation compensators of the technological system of machine tools in order to reduce the time and increase the accuracy of metalworking. The new idea of using active flow compensators is to regulate the flow rate not at the inlet, but at the outlet of the air flow. This design has the energy efficiency that is inherent to a conventional bearing, but the regulation of the lubricant output flow allows the compliance to be reduced to zero and negative values. This article discusses the results of a theoretical study of the static and dynamic characteristics of a two-row radial aerostatic bearing with longitudinal microgrooves and an output flow regulator. Mathematical modeling and theoretical study of stationary modes have been carried out. Formulas for determining static compliance and load capacity are obtained. Iterative finite-difference methods for determining the dynamic characteristics of a structure are proposed. The calculation of dynamic quality criteria was carried out on the basis of the method of rational interpolation of the bearing transfer function, as a system with distributed parameters, developed by the authors. It was found that the volumes of the microgrooves do not have a noticeable effect on the bearing dynamics. It is shown that, in this design, the external combined throttling system is an effective means of maintaining stability and high dynamic quality of the design operating in the modes of low, zero and negative compliance.

Aerostatic bearings are attractive, with minimal friction losses, high durability, and environmental friendliness. However, such designs have a number of disadvantages, including low load-bearing capacity and high compliance due to high air compressibility and limited injection pressure. The article proposes a double-row aerostatic journal bearing with an external combined throttling system and longitudinal microgrooves in the inter-row zone. It is hypothesized that the use of microgrooves will reduce the circumferential flows of compressed air, as a result of which the compliance should decrease and the bearing capacity should increase. To test the hypothesis, we carried out the mathematical modeling, calculations, and theoretical study of stationary operation modes of the bearing for small shaft eccentricities in the vicinity of the central equilibrium position of the shaft and bearing capacity for arbitrary eccentricities. Formulas were obtained for the numerical evaluation of compliance for bearings with a smooth bushing surface and with longitudinal microgrooves. Iterative finite-difference methods for evaluating the fields of the squared pressure are proposed, on the basis of which the load capacity of the bearings is calculated. Experimental verification of the bearing’s theoretical characteristics was carried out, which showed satisfactory agreement between the compared data. The study of the compliance and load capacity of a microgroove bearing yielded impressive results. We show that the positive effect from the application of the improvement begins to manifest itself already at four microgrooves; the effect becomes significant at six microgrooves, and at twelve or more microgrooves, the circumferential flows in the bearing gap practically disappear; therefore, the bearing characteristics can be calculated on the basis of one-dimensional models of air lubrication longitudinal flow. Calculations have shown that for a length of L = 1, the maximum load capacity of a bearing with microgrooves is 1.5 times higher than that of a conventional bearing; for L ≥ 1.5, the bearing capacity increases twice or more. The result obtained allows us to recommend the proposed improvement for practical use in order to increase the load capacity of aerostatic journal bearings significantly.

The disadvantage of aerostatic bearings is their low dynamic quality. The negative impact on the dynamic characteristics of the bearing is exerted by the volume of air contained in the bearing gap, pockets, and microgrooves located at the outlet of the feeding diaphragms. Reducing the volume of air in the flow path is a resource for increasing the dynamic quality of the aerostatic bearing. This article presents an improved design of an axial aerostatic bearing with simple diaphragms, an annular microgroove, and an elastic suspension of the movable center of the supporting disk. A mathematical model is presented and a methodology for calculating the static characteristics of a bearing and dynamic quality indicators is described. The calculations were carried out using dimensionless quantities, which made it possible to reduce the number of variable parameters. A new method for solving linearized and Laplace-transformed boundary value problems for transformants of air pressure dynamic functions in the bearing layer was applied, which made it possible to obtain a numerical solution of problems sufficient for practice accuracy. The optimization of the criteria for the dynamic quality of the bearing was carried out. It is shown that the use of an elastic suspension of the support center improves its dynamic characteristics by reducing the volume of compressed air in the bearing layer and choosing the optimal volume of the microgroove.

Fibroblasts differentiation into myofibroblasts is a central event of tissue fibrosis. Multipotent mesenchymal stromal cells (MSCs) secretome can interfere with fibrosis development; despite precise underlying mechanisms remain unclear. In this study, we tested the hypothesis that MSC secretome can affect fibroblast’ differentiation into myofibroblasts by delivering regulatory RNAs, including microRNAs to these cells. Using the model of transforming growth factor-beta (TGFbeta)-induced fibroblast differentiation into myofibroblasts, we tested the activity of human MSC secretome components, specifically extracellular vesicles (MSC-EV). We showed that MSC-EV down-regulated secretion of extracellular matrix proteins by fibroblasts as well as suppressed their contractility resulting in prevention as well as reversion of fibroblasts differentiation to myofibroblasts. High-throughput sequencing of RNAs extracted from MSC-EV has revealed many fibrosis-associated microRNAs. Fibroblast treatment with MSC-EV led to direct transfer of microRNAs, which resulted in the elevation of most prominent fibrosis-associated microRNAs, including microRNA-21 and microRNA-29c. Using MSC-EV transfection by antagomirs to these microRNAs we demonstrated their involvement in the suppression of fibroblast differentiation in our model. Taken together, MSC secretome can suppress fibrosis by prevention of fibroblast differentiation into myofibroblasts as well as induce de-differentiation of the latter by direct transfer of specific microRNAs.

Background: Differences in demographic behaviours across countries and subnational regions have stimulated interest in studying the relationships between individual characteristics and the contexts in which individuals are embedded. Analytical approaches that include contextual indicators in statistical analyses of demographic behaviour need well-documented comparative data at the national and the subnational regional level. The Contextual Database (CDB) of the Generations and Gender Programme (GGP; http://www.ggp-i.org/data/ggp-contextual-database) supports such analyses by providing comparative data on demographic and socio-economic contexts in up to 60 countries in Europe, North America, Asia, and Oceania. Objective: This paper presents conceptual considerations and an overview of the content and the functionality of the CDB. Research examples illustrate how data from this database can increase the analytical potential of demographic analyses. Conclusions: The CDB is a state-of-the-art research tool that provides well-documented comparative data at the national and the subnational regional level. Although it is conceptually linked to the Generations and Gender Survey (GGS), it can also be used to analyse data from other surveys, to study macro developments, and for teaching and lecturing. The CDB has a number of valuable features. First, it has a large number of indicators specifically geared towards demographic analyses, which provide extensive temporal and geographic coverage. Second, its dynamic web environment provides a high degree of transparency on data sources, as it offers meta-data for each individual entry. Finally, the CDB supports geocoding schemes that are used by the GGS and other surveys to denote region and country of residence.

Based on data from five cross-sectional household surveys conducted during 1996-2007, this study provides initial results of an analysis of self-perceived health in Belarus. The findings suggest that there has been a compression of morbidity. Self-perceived health has been improving steadily for both sexes and at all ages. Despite this notable improvement, Belarus still remains far behind Western Europe in terms of healthy life expectancy. This disadvantage is mainly due to higher mortality among the working-age population, but health at older ages also plays an important role. Education appears to be the most important factor associated with self-rated health.