Physiologic isolation and expansion of human mesenchymal stem/stromal cells for manufacturing of cell-based therapy products

The utilization of mesenchymal stem/stromal cells raises new hopes in treatment of diseases and pathological conditions, while at the same time bringing immense challenges for researchers, manufacturers and physicians. It is essential to consider all steps along the in vitro fabrication of cell-based products in order to reach efficient and reproducible treatment outcomes. Here, the optimal protocols for isolation, cultivation and differentiation of mesenchymal stem cells are required. In this review we discuss these aspects and their influence on the final cell-based product quality. We demonstrate that physiological in vitro cell cultivation conditions play a crucial role in therapeutic functionalities of cultivated cells. We show that three-dimensional cell culture, dynamic culture conditions and physiologically relevant in vitro oxygen concentrations during isolation and expansion make a decisive contribution towards the improvement of cell-based products in regenerative medicine

A deployment-friendly decentralized scheduling approach for cooperative multi-agent systems in production systems

Abstract Decentralized control paradigms are becoming more and more attractive in an ever-changing commercial environment, where there is a strong trend towards smaller production lot sizes. Whereas centralized scheduling might find a global throughput optimum (even at high computational and implementation cost), decentralized scheduling decisions in a multi-agent system are much more manageable and agents are more robust to handle any interruptions that might take place on the production floor. Compared to a centralised architecture, the development, testing and commissioning is definitely more complex, as it requires the availability of the physical units. Yet these aspects are not visited frequently by research activities. This paper details a novel implementation approach of a multi-agent based production control, that was developed for a lab-contained production environment that serves as test-bed for decentralized scheduling algorithms, with both a nominal operational mode and a simulation mode. The latter one is introduced to ease up the deployment process of the system. The description of the new approach is illustrated with different examples

Dynamic cultivation of mesenchymal stem cell aggregates

Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions\u2014such as hypoxia, three-dimensional environments, and dynamic cultivation\u2014prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates

Praktikumsbegleitende Weblogs: Ein geeignetes Mittel im Umgang mit Stress?

In Praktika gilt der Einsatz von Weblogs als naheliegendes Mittel zur Förderung von Reflexion und Kommunikation. Besondere Potenziale werden Weblogs im Hinblick auf Stressverarbeitung zugeschrieben. Bislang ist jedoch unklar, ob dieser Ansatz für alle Studierenden gleichermaßen geeignet ist. In dem empirischen Beitrag wird der Frage nachgegangen, unter welchen Bedingungen das tägliche Bloggen bei N=141 angehenden Lehrpersonen im Praktikum von diesen als sinnvoll erachtet wird. Die Ergebnisse zeigen, dass nur eine Minderheit das Bloggen als hilfreich beurteilt. Positivere Einschätzungen zeigen sich bei Personen mit höheren Werten in Offenheit, Neurotizismus, Stresslevel und Leistungsbereitschaft. 29.01.2016 | Nives Egger, Alexandra Totter & Dominik Petko (Goldau, Zürich

Intelligent workpiece carrier for distributed data collection and control in manufacturing environments

Abstract The growing demand for customized products is challenging companies to change their organizational structure towards a flexible organizational model. However, small and medium sized enterprises (SME) do not have the necessary resources to integrate in their production processes new technologies which could help them facing such challenges. We propose a framework in which an intelligent workpiece carrier (IWC) is introduced in a traditional production line. We propose to integrate the knowledge of production steps in the IWC to make it able to take decisions about the process execution. A first prototype was developed and tested to verify the effectiveness of the proposed framework. Through the implementation, it has been shown that the IWC represents a promising component in the realization of flexible production systems

Online-Reflexion mittels Weblogs: Ein Mittel zur Auseinandersetzung mit belastenden Situationen in der berufspraktischen Ausbildung von Lehrpersonen?

Weblogs werden grosse Potenziale zur Reflexion von Erfahrungen und belastenden Situationen in der berufspraktischen Ausbildung von Lehrpersonen zugeschrieben. In einer Studie wurde deshalb an zwei pädagogischen Hochschulen untersucht, ob Studierende unterschiedliche Facetten des Bloggens nach einem vierwöchigen Praktikum als hilfreich erleben. Die Ergebnisse zeigen, dass nur eine Minderheit das Verfassen von Blogbeiträgen positiv beurteilt. Als hilfreich werden allerdings gegenseitige Feedbacks erlebt. Wenn Weblogs als verbindlicher Teil des Leistungsauftrags eingesetzt werden, zeigen sich in der Tendenz positivere Einschätzungen als bei freiwilligem Bloggen.Weblogs are considered to have great potential for supporting reflection on experiences and stressful situations during teaching internships. In this study, students from two universities of teacher education were asked to assess different aspects of blogging with respect to its usefulness after a four-week internship. The results show that only a minority assessed weblog writing positively. However, interpersonal feedback on blog postings was found to be useful. In addition, when weblog writing is mandatory, there is a trend of it being assessed more positively than voluntary weblog writing

Comparison of nutritional composition between plant-based drinks and cow’s milk

The high decline in liquid milk consumption in Western countries has been compensated by the increased consumption of processed dairyproducts and the rapidly increasing number of new plant-based beverages constantly introduced in the market, advertised as milk substitutes and placed on shelves near milk products. To provide better understanding about the nutritional value of these drinks compared with cow’s milk, 27 plant-based drinks of 8 different species and two milk samples were purchased from two big retailers in Switzerland, and their composition regarding protein, carbohydrate, fat, vitamin, and mineral contents and residue load [glyphosate, aminomethylphosphonic acid (AMPA), and arsenic] was analyzed quantitatively and qualitatively. Energy and nutrient intakes were calculated and compared with the dietary reference values for Germany, Austria and Switzerland (D-A-CH). In addition, the digestible indispensable amino acid score (DIAAS) was calculated to estimate the quality of the proteins. Milk contained more energy; fat; carbohydrate; vitamins C, B2, B12, and A; biotin; pantothenic acid; calcium; phosphorus; and iodine than most plant-based drinks. Soy drinks provided slightly more proteinand markedly more vitamins B1 and B6, folic acid, and vitamins E and D2 (with supplemented vitamin D2) and K1, magnesium, manganese, iron, and copper than milk and the other plant-based drinks. However, with the exception of cow’s milk and soy drinks, which had > 3% protein, most milk alternatives contained � 1% protein; therefore, they cannot be considered good protein sources. In regard to protein quality, milk was outstanding compared with all plant-based drinks and exhibited higher calculated DIAASs. Our results show that the analyzed plant-based drinks are not real alternatives to milk in terms of nutrient composition, even if the actual fortification is taken into account. Improved fortification is still an issue and can be optimized using the most bioavailable and soluble derivatives. Complete replacement of milk with plant-based drinks without adjusting the overall diet can lead to deficiencies of certain important nutrients in the long term

Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase II trial.

BACKGROUND In intermediate-risk non-muscle invasive bladder cancer (NMIBC) clinical guidelines suggest an adjuvant instillation with a chemotherapeutic agent. However, the agent and regimen are not clearly defined. Worldwide, less than 15% of patients receive this adjuvant chemotherapeutic instillation. We recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In this phase II trial, we aim to use our in vitro pipeline to select the most effective drug for chemotherapeutic instillation in NMIBC patients. METHODS Patients with first diagnosis of intermediate-risk NMIBC that are directed to transurethral resection of bladder tumor (TURBT) are enrolled. During TURBT, tumor is sampled, and specimens are directed to generate PDO. Once the PDO are formed, drug screens on them for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel are performed. The drug with the highest antitumor activity in vitro will then be selected for 6 adjuvant intravesical instillations once weekly. Thereafter, patients are followed according to clinical guidelines by cystoscopy. DISCUSSION The aim of this trial is to use drug screens in PDO to precise treatment selection for adjuvant instillation therapies in patients with intermediate-risk NMIBC. The ultimate goal of this trial is to reduce the risk of cancer recurrence. In the future, we aim to conduct clinical multicenter trials with an increased sample size, a broader panel of compounds and a focus on the reduction of cancer recurrence by precision delivery of care. Trial registration NCT05024734