Differentiation potential of human postnatal mesenchymal stem cells, mesoangioblasts, and multipotent adult progenitor cells reflected in their transcriptome and partially influenced by the culture conditions
Roobrouck V.D.,Catholic University of Leuven |
Carlos Clavel,Catholic University of Leuven |
Jacobs S.A.,Catholic University of Leuven |
Ulloa-Montoya F.,Catholic University of Leuven |
And 9 more authors.
Stem Cells | Year: 2011
Several adherent postnatal stem cells have been described with different phenotypic and functional properties. As many of these cells are being considered for clinical therapies, it is of great importance that the identity and potency of these products is validated. We compared the pheno-type and functional characteristics of human mesenchymal stem cells (hMSCs), human mesoangioblasts (hMab), and human multipotent adult progenitor cells (hMAPCs) using uniform standardized methods. Human MAPCs could be expanded significantly longer in culture. Differences in cell surface marker expression were found among the three cell populations with CD140b being a distinctive marker among the three cell types. Differentiation capacity towards adipocytes, osteoblasts, chondrocytes, and smooth muscle cells in vitro, using established protocols, was similar among the three cell types. However, only hMab differentiated to skeletal myocytes, while only hMAPCs differentiated to endothelium in vitro and in vivo. A comparative transcriptome analysis confirmed that the three cell populations are distinct and revealed gene signatures that correlated with their specific functional properties. Furthermore, we assessed whether the phenotypic, functional, and transcriptome features were mediated by the culture conditions. Human MSCs and hMab cultured under MAPC conditions became capable of generating endothelial-like cells, whereas hMab lost some of their ability to generate myotubes. By contrast, hMAPCs cultured under MSC conditions lost their endothelial differentiation capacity, whereas this was retained when cultured under Mab conditions, however, myogenic capacity was not gained under Mab conditions. These studies demonstrate that hMSCs, hMab, and hMAPCs have different properties that are partially mediated by the culture conditions. © AlphaMed Press.
Swamidass S.J.,University of Washington |
Matlock M.,University of Washington |
Rozenblit L.,Prometheus Research
PLoS ONE | Year: 2015
Many scientific questions are best approached by sharing data-collected by different groups or across large collaborative networks-into a combined analysis. Unfortunately, some of the most interesting and powerful datasets-like health records, genetic data, and drug discovery data-cannot be freely shared because they contain sensitive information. In many situations, knowing if private datasets overlap determines if it is worthwhile to navigate the institutional, ethical, and legal barriers that govern access to sensitive, private data. We report the first method of publicly measuring the overlap between private datasets that is secure under a malicious model without relying on private protocols or message passing. This method uses a publicly shareable summary of a dataset's contents, its cryptoset, to estimate its overlap with other datasets. Cryptosets approach "information-theoretic" security, the strongest type of security possible in cryptography, which is not even crackable with infinite computing power. We empirically and theoretically assess both the accuracy of these estimates and the security of the approach, demonstrating that cryptosets are informative, with a stable accuracy, and secure. © 2015 Swamidass et al.
Johnson S.B.,Columbia University |
Johnson S.B.,Simons Foundation |
Whitney G.,Simons Foundation |
McAuliffe M.,U.S. National Institutes of Health |
And 4 more authors.
Journal of the American Medical Informatics Association | Year: 2010
Objective: To propose a centralized method for generating global unique identifiers to link collections of research data and specimens. Design: The work is a collaboration between the Simons Foundation Autism Research Initiative and the National Database for Autism Research. The system is implemented as a web service: an investigator inputs identifying information about a participant into a client application and sends encrypted information to a server application, which returns a generated global unique identifier. The authors evaluated the system using a volume test of one million simulated individuals and a field test on 2000 families (over 8000 individual participants) in an autism study. Measurements: Inverse probability of hash codes; rate of false identity of two individuals; rate of false split of single individual; percentage of subjects for which identifying information could be collected; percentage of hash codes generated successfully. Results: Large-volume simulation generated no false splits or false identity. Field testing in the Simons Foundation Autism Research Initiative Simplex Collection produced identifiers for 96% of children in the study and 77% of parents. On average, four out of five hash codes per subject were generated perfectly (only one perfect hash is required for subsequent matching). Discussion: The system must achieve balance among the competing goals of distinguishing individuals, collecting accurate information for matching, and protecting confidentiality. Considerable effort is required to obtain approval from institutional review boards, obtain consent from participants, and to achieve compliance from sites during a multicenter study. Conclusion: Generic unique identifiers have the potential to link collections of research data, augment the amount and types of data available for individuals, support detection of overlap between collections, and facilitate replication of research findings.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 266.88K | Year: 2015
DESCRIPTION provided by applicant Electronic data capture EDC systems have increasingly replaced paper based methods of collecting mental health research data As EDC systems have proliferated however so has the number of incompatible formats for storing EDC instruments form configurations The lack of interoperability among EDC formats makes it difficult to reuse share or find previously configured instruments unless they were configured for the same EDC system Currently the primary approach to this problem is to manually reconfigure the instruments in the target EDC system a highly inefficient use of human and financial resources Ideally each research instrument would need to be configured only once would be stored in an easily accessible place for others to use and would work seamlessly with its usersandapos EDC tools The proposed project will bring this ideal closer to reality by laying the groundwork for an interoperable ecosystem of mental health research instruments The first step is to create the Portable Research Instrument Standard for Mental Health PRISMH an open metadata standard for representing mental health research instruments that does not depend on any EDC system or device Aim PRISMH will make it possible to develop software that can convert instruments between PRISMH and the formats used by four specific EDC systems Research Electronic Data Capture REDCap Qualtrics and Prometheus Researchandapos s EDC systems RexEntry and RexSurvey Aim We will collaborate with the Center for Open Science COS to bundle PRISMH and the format conversion tools into an andquot add onandquot module for the COSandapos s free web based scientific collaboration platform the Open Science Framework OSF This will connect PRISMH and the conversion tools to the OSFandapos s existing infrastructure for finding curating and sharing collections of digital research artifacts such a instrument configuration files Aim Finally we will modify the EDC form building tool embedded in RexDB our web based data management platform for mental health researchers so users can search for accessible instrument configurations stored in OSF projects import those of interest into RexDB for editing and reuse and share locally configured instruments with accessible OSF projects The standards and tools that Prometheus Research and the COS will build through this project will have transformative potential for mental health research It will give the mental health research community access to freely available tools that empower them to reuse share and find mental health research instruments accelerating research by saving time money and frustration Use of this network of standards and tools will remove critical bottlenecks in the execution of NIMH funded research increasing the NIHandapos s and the publicandapos s return on investment while improving the ability of scientists to focus on collecting high quality data Finally this project will improve Prometheus Researchandapos s commercialization potential by funding the development of features critical to a low cost self service version of the RexDB that will be marketable to a broad segment of the research data management market PUBLIC HEALTH RELEVANCE Mental health researchers inadvertently waste time and money because there is no common standard for configuring electronic data collection forms making it difficult for them to share reuse and find the forms they need In this project we aim to facilitate these tasks by creating new open source tools and standards which will be integrated into an existing web based platform for managing research materials These improvements will benefit researchers funding agencies and the public through decreased costs and delays in mental health research
Prometheus Research | Date: 2012-02-10
A method may include receiving a syntactic database query for retrieving information, where the syntactic database query may include two or more tokens. A subset of the two or more tokens may include a nested aggregation, and the nested aggregation may include at least (a) a first aggregate expression including a first aggregate function, a first base, and a first range, and (b) a second aggregate expression including a second aggregate function, a second base and a second range, where the second range includes the first aggregate expression. The method may further include parsing the two or more of tokens, where parsing includes identifying at least a first query context and a second query context.
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 136.50K | Year: 2010
This Small Business Innovation Research (SBIR) Phase I project is to develop a product that enables automated access to any relational database via the web - a web-browser for non-technical users; XML/JSON/CSV for more technical users who wish to use the data in their own applications. The system will first intergotate and determine a database's contents and allow the owner to select access levels. Researchers can then interact with the data or share references to data sets with a URL. The key innovation is a systematic scheme for automatically mapping any relational database into a set of URLs. Successful completion of this project will liberate valuable data trapped in research systems for collaboration and analysis. While tools exist for web-enabling specific databases, most are designed for database administrators or developers. The Prometheus Internet Database Server will target non-technical users who need to focus on research instead of technical problems. Unlike existing solutions that are designed for specific products, Prometheus' system will be based on open source technology for use with data sources of unknown type and quality. As a result, researchers and the general public can utilize the Internet to access and disseminate disparate data that is currently stored in multiple databases - a task that cannot readily be accomplished by currently-available products.
PubMed | Catholic University of Leuven, Prometheus Research and Terumo BCT Inc.
Type: Journal Article | Journal: Cytotherapy | Year: 2016
With the increasing scale in stem cell production, a robust and controlled cell expansion process becomes essential for the clinical application of cell-based therapies. The objective of this work was the assessment of a hollow fiber bioreactor (Quantum Cell Expansion System from Terumo BCT) as a cell production unit for the clinical-scale production of human periosteum derived stem cells (hPDCs).We aimed to demonstrate comparability of bioreactor production to standard culture flask production based on a product characterization in line with the International Society of Cell Therapy in vitro benchmarks and supplemented with a compelling quantitative in vivo bone-forming potency assay. Multiple process read-outs were implemented to track process performance and deal with donor-to-donor-related variation in nutrient needs and harvest timing.The data show that the hollow fiber bioreactor is capable of robustly expanding autologous hPDCs on a clinical scale (yield between 316 million and 444 million cells starting from 20 million after8 days of culture) while maintaining their in vitro quality attributes compared with the standard flask-based culture. The in vivo bone-forming assay on average resulted in 10.33.7% and 11.03.8% newly formed bone for the bioreactor and standard culture flask respectively. The analysis showed that the Quantum system provides a reproducible cell expansion process in terms of yields and culture conditions for multiple donors.
Prometheus Research | Date: 2012-08-08
Computer Software for Database Management; Computer Software Platforms for Database Catalogue Library; Computer Software for Creating Searchable Databases of Information and Data.
PubMed | Catholic University of Leuven, Prometheus Research, University College London and University of Liège
Type: | Journal: Biomaterials | Year: 2016
The development of osteoinductive calcium phosphate- (CaP) based biomaterials has, and continues to be, a major focus in the field of bone tissue engineering. However, limited insight into the spatiotemporal activation of signalling pathways has hampered the optimisation of invivo bone formation and subsequent clinical translation. To gain further knowledge regarding the early molecular events governing bone tissue formation, we combined human periosteum derived progenitor cells with three types of clinically used CaP-scaffolds, to obtain constructs with a distinct range of bone forming capacity invivo. Protein phosphorylation together with gene expression for key ligands and target genes were investigated 24hours after cell seeding invitro, and 3 and 12 days post ectopic implantation in nude mice. A computational modelling approach was used to deduce critical factors for bone formation 8 weeks post implantation. The combined Ca(2+)-mediated activation of BMP-, Wnt- and PKC signalling pathways 3 days post implantation were able to discriminate the bone forming from the non-bone forming constructs. Subsequently, a mathematical model able to predict in vivo bone formation with 96% accuracy was developed. This study illustrates the importance of defining and understanding CaP-activated signalling pathways that are required and sufficient for invivo bone formation. Furthermore, we demonstrate the reliability of mathematical modelling as a tool to analyse and deduce key factors within an empirical data set and highlight its relevance to the translation of regenerative medicine strategies.