Summary of project PR001357

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001357. The data can be accessed directly via it's Project DOI: 10.21228/M89Q66 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001357
Project DOI:doi: 10.21228/M89Q66
Project Title:A Metabolomics-guided Bioreactor for Improved Engineered Bone Implants (BioImplant)
Project Type:NMR-based untargeted metabolomics
Project Summary:In an “omic” era, metabolomics offers exquisite insight into the complex metabolic network of living organisms and their adaptation mechanisms towards disease, therapy and environment. Metabolic markers (sets of metabolites) are emerging as new means of diagnostics, personalized follow-up and prediction of patient health status. Here, metabolomics is used for the first time to guide the development of a stem cell (SC) bioreactor to produce improved quality bone tissue for implantation. 3D porous scaffolds will be produced using biodegradable polymer poly-L-lactic acid (PLLA), both bare and collagen-coated to improve cell adhesion. These scaffolds will be 3D-printed with controlled architectures (both internally and externally), namely with struts alignment of 90o, with and without offset, expected to trigger distinct biological behaviors, particularly under mechanical cues. Scaffolds will be tested in a bioreactor for growth and differentiation of human mesenchymal SCs (hMSCs) into osteogenic lineage. hMSCs obtained from adipose tissue or bone marrow will be compared, as they have shown secretome differences and possible different potentials for osteogenic differentiation. The bioreactor will allow the application of controlled compression, to help mimic bone physiological conditions, and scaffold piezoelectricity will be studied in the same context. Scaffolds and physical cues will be tested in vitro (in osteogenic media) and monitored by biological measurements (proliferation, viability, differentiation indicators) and, for the first time, by cell metabolomics to identify the impact of each variable (scaffold composition, morphology, piezoelectricity and compression) on hMSC metabolism and define metabolic markers of hMSC function. Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of cell extracts will identify dynamic metabolic cellular profiles associated to i) hMSC self-renewal and differentiation mechanisms, and their adaptations to ii) scaffold characteristics and iii) physical cues (compression and/or piezoelectricity). Statistical correlation of metabolic profiles with scaffold/bioreactor features and biological parameters will unveil metabolic markers of bioreactor performance and novel knowledge on SC osteogenic metabolism. Key metabolites will be identified as potentially osteogenesis-inducing, a role to be demonstrated using metabolite-tailored cell media to potentially substitute osteogenic growth factors and, thus, tackle related implantation challenges. Putative hypotheses of responsive hMSCs metabolic pathways will be validated through pathway network analysis, isotope-labeled tracers (NMR) and specific protein and genetic measurements. To our knowledge, this project proposes the first use of metabolomics to guide in vitro bone tissue engineering, building on recent proposals to exploit “omics” to understand, monitor and guide SC behavior for effective tissue engineering and implantation.
Institute:University of Aveiro
Department:Department of Chemistry
Laboratory:CICECO - Aveiro Institute of Materials
Last Name:Bispo
First Name:Daniela S.C.
Address:Campus Universitário de Santiago, Aveiro, Aveiro, Aveiro, 3810-193, Portugal
Email:d.bispo@ua.pt
Phone:none
Funding Source:The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) for co-funding the BIOIMPLANT project (PTDC/BTM-ORG/28835/2017) through the COMPETE2020 program and European Union fund FEDER (POCI-01-0145-FEDER-028835). CSHJ is grateful to the same project for funding her contract with the University of Aveiro. DSB acknowledges the Sociedade Portuguesa de Química and FCT for her PhD grant SFRH/BD/150655/2020. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). The NMR spectrometer used in this work is part of the National NMR Network (PTNMR) and, partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).

Summary of all studies in project PR001357

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST002142 Endo- and Exometabolome Crosstalk in Mesenchymal Stem Cells Undergoing Osteogenic Differentiation (Lipid Samples) Homo sapiens University of Aveiro NMR* 2022-05-02 1 15 Uploaded data (14.5M)*
ST002143 Endo- and Exometabolome Crosstalk in Mesenchymal Stem Cells Undergoing Osteogenic Differentiation (Media Samples) Homo sapiens University of Aveiro NMR* 2022-05-02 1 28 Uploaded data (57.1M)*
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