Stem cells are of widespread interest in regenerative medicine due to their capability of self-renewal and differentiation, which is regulated by their three-dimensional microenvironment. In this study, a computer-aided biofabrication technique based on laser-induced forward transfer (LIFT) is used to generate grafts consisting of mesenchymal stem cells (MSCs). We demonstrate that (i) laser printing does not cause any cell damage; (ii) laser-printed MSC grafts can be differentiated toward bone and cartilage; (iii) LIFT allows printing of cell densities high enough for the promotion of chondrogenesis; (iv) with LIFT three-dimensional scaffold-free autologous tissue grafts can be fabricated keeping their predefined structure, and (v) predifferentiated MSCs survived the complete printing procedure and kept their functionality. We believe that our results will find important applications in stem cell biology and tissue engineering.
The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON’s goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36–62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04768998.https://clinicaltrials.gov/ct2/show/NCT04747366.https://clinicaltrials.gov/ct2/show/NCT04679584
Regenerative medicine is in need of solid, large animal models as a link between rodents and humans to evaluate the functionality, immunogenicity, and clinical safety of stem cell-derived cell types. The common marmoset (Callithrix jacchus) is an excellent large animal model, genetically close to humans and readily used worldwide in clinical research. Until now, only two groups showed the generation of induced pluripotent stem cells (iPSCs) from the common marmoset using integrating retroviral vectors. Therefore, we reprogrammed bone marrow-derived mesenchymal cells (MSCs) of adult marmosets in the presence of TAV, SB431542, PD0325901, and ascorbic acid via a novel, excisable lentiviral spleen focus-forming virus (SFFV)-driven quad-cistronic vector system (OCT3/4, KLF4, SOX2, C-MYC). Endogenous pluripotency markers like OCT3/4, KLF4, SOX2, C-MYC, LIN28, NANOG, and strong alkaline phosphatase signals were detected. Exogenous genes were silenced and additionally the cassette was removed with a retroviral Gag precursor system. The cell line could be cultured in absence of leukemia inhibitory factor (LIF) and basic fibroblast growth factor (bFGF) and could be successfully differentiated into embryoid bodies and teratomas with presence of all three germ layers. Directed differentiation generated neural progenitors, megakaryocytes, adipocytes, chondrocytes, and osteogenic cells. Thus, all criteria for fully reprogrammed bone marrow-MSCs of a nonhuman primate with a genetically sophisticated construct could be demonstrated. These cells will be a promising tool for future autologous transplantations.
BackgroundParticipation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly.MethodsMales and females between 65 and 80 years of age (N = 5582) were randomly selected from the residents’ registration office in Hannover, Germany, and were invited to participate in a study featuring vaccination with a seasonal adjuvanted influenza vaccine (Fluad™, Novartis) including five follow-up visits (day 0, 1/3, 7, 21, 70 with respect to vaccination). A 24-item nonresponder questionnaire, including 10 items on reasons for participating in a hypothetical health study, was mailed to 1500 randomly selected nonparticipants. The same 10 items were included in the end-of-study questionnaire administered to the participants in the vaccination study (n = 200). Logistic regression analysis with backward elimination was used to identify the reasons most strongly associated with nonparticipation.ResultsFive hundred thirty-one (35%) nonparticipants and 200 participants (100%) returned the respective questionnaires. Nonparticipation was associated with a lower interest in obtaining personal health information (OR = 3.32) and a preference for less invasive (OR = 3.01) and less time-demanding (OR = 2.19) studies. Responses to other items, e.g. regarding altruistic motives, monetary compensation, general interest of the study, or study approval through ethics committee and data security authority, did not differ between participants and nonparticipants.ConclusionsParticipation rates in health studies among elderly individuals could potentially be improved by reducing interventions and time demand, for instance by implementing methods of self-sampling and remote data collection.Trial registrationNo. 1100359 (ClinicalTrials.gov, date of registration: 09.02.2015).Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-017-0302-z) contains supplementary material, which is available to authorized users.
Biobanks are the basis for a substantial part of biomedical research. The development, establishment and operation of biobanks are connected to a broad range of aspects, mainly concerning the preparation, storage, usage and dissemination of samples and associated data, in addition to the social and public involvement of these processes. These complex requirements can often only be managed in large centralized biobanks. In recent years, centralized clinical biobanks have been established in several university clinics in Germany. Similar activities take place in other European countries and worldwide. This article highlights the requirements and main tasks of centralized clinical biobanks: high-quality pre-analytics and sample storage, the creation of professional IT structures, data protection, ethical issues, in addition to quality and project management.
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