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Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides

BACKGROUND: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SP...

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Autores principales: van Buul, Gerben M., Kotek, Gyula, Wielopolski, Piotr A., Farrell, Eric, Bos, P. Koen, Weinans, Harrie, Grohnert, Anja U., Jahr, Holger, Verhaar, Jan A. N., Krestin, Gabriel P., van Osch, Gerjo J. V. M., Bernsen, Monique R.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044153/
https://www.ncbi.nlm.nih.gov/pubmed/21373640
http://dx.doi.org/10.1371/journal.pone.0017001
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author van Buul, Gerben M.
Kotek, Gyula
Wielopolski, Piotr A.
Farrell, Eric
Bos, P. Koen
Weinans, Harrie
Grohnert, Anja U.
Jahr, Holger
Verhaar, Jan A. N.
Krestin, Gabriel P.
van Osch, Gerjo J. V. M.
Bernsen, Monique R.
author_facet van Buul, Gerben M.
Kotek, Gyula
Wielopolski, Piotr A.
Farrell, Eric
Bos, P. Koen
Weinans, Harrie
Grohnert, Anja U.
Jahr, Holger
Verhaar, Jan A. N.
Krestin, Gabriel P.
van Osch, Gerjo J. V. M.
Bernsen, Monique R.
author_sort van Buul, Gerben M.
collection PubMed
description BACKGROUND: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. METHODOLOGY/PRINICIPAL FINDINGS: Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. CONCLUSIONS: SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.
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spelling pubmed-30441532011-03-03 Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides van Buul, Gerben M. Kotek, Gyula Wielopolski, Piotr A. Farrell, Eric Bos, P. Koen Weinans, Harrie Grohnert, Anja U. Jahr, Holger Verhaar, Jan A. N. Krestin, Gabriel P. van Osch, Gerjo J. V. M. Bernsen, Monique R. PLoS One Research Article BACKGROUND: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. METHODOLOGY/PRINICIPAL FINDINGS: Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. CONCLUSIONS: SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects. Public Library of Science 2011-02-23 /pmc/articles/PMC3044153/ /pubmed/21373640 http://dx.doi.org/10.1371/journal.pone.0017001 Text en van Buul et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
van Buul, Gerben M.
Kotek, Gyula
Wielopolski, Piotr A.
Farrell, Eric
Bos, P. Koen
Weinans, Harrie
Grohnert, Anja U.
Jahr, Holger
Verhaar, Jan A. N.
Krestin, Gabriel P.
van Osch, Gerjo J. V. M.
Bernsen, Monique R.
Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title_full Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title_fullStr Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title_full_unstemmed Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title_short Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides
title_sort clinically translatable cell tracking and quantification by mri in cartilage repair using superparamagnetic iron oxides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044153/
https://www.ncbi.nlm.nih.gov/pubmed/21373640
http://dx.doi.org/10.1371/journal.pone.0017001
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