Comparative Analysis of Mesenchymal Stem Cell Cultivation in Fetal Calf Serum, Human Serum, and Platelet Lysate in 2D and 3D Systems

In vitro two-dimensional (2D) and three-dimensional (3D) cultivation of mammalian cells requires supplementation with serum. Mesenchymal stem cells (MSCs) are widely used in clinical trials for bioregenerative medicine and in most cases, in vitro expansion and differentiation of these cells are required before application. Optimized expansion and differentiation protocols play a key role in the treatment outcome. 3D cell cultivation systems are more comparable to in vivo conditions and can provide both, more physiological MSC expansion and a better understanding of intercellular and cell-matrix interactions. Xeno-free cultivation conditions minimize risks of immune response after implantation. Human platelet lysate (hPL) appears to be a valuable alternative to widely used fetal calf serum (FCS) since no ethical issues are associated with its harvest, it contains a high concentration of growth factors and cytokines and it can be produced from expired platelet concentrate. In this study, we analyzed and compared proliferation, as well as osteogenic and chondrogenic differentiation of human adipose tissue-derived MSCs (hAD-MSC) using three different supplements: FCS, human serum (HS), and hPL in 2D. Furthermore, online monitoring of osteogenic differentiation under the influence of different supplements was performed in 2D. hPL-cultivated MSCs exhibited a higher proliferation and differentiation rate compared to HS- or FCS-cultivated cells. We demonstrated a fast and successful chondrogenic differentiation in the 2D system with the addition of hPL. Additionally, FCS, HS, and hPL were used to formulate Gelatin-methacryloyl (GelMA) hydrogels in order to evaluate the influence of the different supplements on the cell spreading and proliferation of cells growing in 3D culture. In addition, the hydrogel constructs were cultivated in media supplemented with three different supplements. In comparison to FCS and HS, the addition of hPL to GelMA hydrogels during the encapsulation of hAD-MSCs resulted in enhanced cell spreading and proliferation. This effect was promoted even further by cultivating the hydrogel constructs in hPL-supplemented media

TRANSIT Working Paper # 7

A previous version of this paper has been part of TRANSIT Deliverable 3.3 (July 2016), the second prototype of TSI theory.[Abstract] This working paper presents a set of propositions about the agency and dynamics of transformative social innovation (TSI) that have been developed as part of an EU-funded research project entitled “TRANsformative Social Innovation Theory” (TRANSIT; 2014-2017). These TSI propositions represent first steps towards the development of a new theory of TSI, taking the form of proto-explanations of the agency and dynamics of TSI, based on the bringing together of our empirical observations on TSI and the project's theoretical reviews and theoretical framings. Ideally this working paper should be read in conjunction with the working paper entitled “A framework for transformative social innovation” (Haxeltine et al 2016) which presents in skeletal terms the theoretical and conceptual framing of TSI developed in the TRANSIT project. This TSI framework builds on sustainability transition studies, social innovation research, social psychology studies of empowerment and other several other areas of social theory to deliver a bespoke theoretical and conceptual framework that is grounded in a relational ontology and which is being employed as a platform for the development of a middle-range theory of TSI. Next we provide a very brief overview of some key elements of the framework, in particular how we conceptualise social innovation, transformative change, and transformative social innovation. Propositions were developed for each of four relational dimensions implied by the TSI framework with also a brief statement of the topic addressed by each of the twelve propositions.This article is based on research carried out as part of the Transformative Social Innovation Theory (“TRANSIT”) project, which is funded by the European Union's Seventh Framework Programme (FP7) under grant agreement 61316

Transformative Change for an Inclusive Society: Insights from Social Innovations and Implications for Policy Innovation and innovation Policy

Our societies experience challenges of inclusion and cohesion and suffer (evidently) from multiple problems associated with exclusion across economic, social, political and many other dimensions. The challenge of building more inclusive societies is recognized at highest policy levels. The Europe 2020 Strategy (EC, 2010) has smart, inclusive and sustainable growth as its overarching aim, for example. Yet, against the backdrop of a widening and intensifying set of inclusion challenges, conventional inclusion policies, until now based heavily around economic growth,skilling and full employment, struggle to make our societies more inclusive. In this context, it is insightful to look toward social innovation movements, several of which organize around agendas of inclusion and are critical of mainstream systems and policies, to see what they bring to societal discourse and action on the issues of in/exclusion. This is important especially in relation to mainstream systems that are under stress and struggle to be inclusive, especially the market economy, social welfare systems, representative democracy, and workfare policies. Social innovations are being studied in the TRANSIT Project, which aims to develop a theory of societally transformative social innovation. What insights do TRANSIT Project empirics offer into the potential of our studied social innovations to support transformative change toward more inclusive societies? What insights do they offer for innovation policies and inclusion policies? Can we improve our developing theory of social innovation in relation to transformative societal change by examining social innovation cases using the lens and probe of in/exclusion

On the agency and dynamics of transformative social innovation: TRANSIT working paper 7

info:eu-repo/semantics/publishe

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified