title: Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells chondrogenic differentiation: a multi-scale in vitro study.
abstract: OBJECTIVE
  The aim of this work was the development of successful cell therapy techniques for cartilage engineering. This will depend on the ability to monitor non-invasively transplanted cells, especially mesenchymal stem cells (MSCs) that are promising candidates to regenerate damaged tissues.
  
  
  METHODS
  MSCs were labeled with superparamagnetic iron oxide particles (SPIO). We examined the effects of long-term labeling, possible toxicological consequences and the possible influence of progressive concentrations of SPIO on chondrogenic differentiation capacity.
  
  
  RESULTS
  No influence of various SPIO concentrations was noted on human bone marrow MSC viability or proliferation. We demonstrated long-term (4 weeks) in vitro retention of SPIO by human bone marrow MSCs seeded in collagenic sponges under TGF-β1 chondrogenic conditions, detectable by Magnetic Resonance Imaging (MRI) and histology. Chondrogenic differentiation was demonstrated by molecular and histological analysis of labeled and unlabeled cells. Chondrogenic gene expression (COL2A2, ACAN, SOX9, COL10, COMP) was significantly altered in a dose-dependent manner in labeled cells, as were GAG and type II collagen staining. As expected, SPIO induced a dramatic decrease of MRI T2 values of sponges at 7T and 3T, even at low concentrations.
  
  
  CONCLUSIONS
  This study clearly demonstrates (1) long-term in vitro MSC traceability using SPIO and MRI and (2) a deleterious dose-dependence of SPIO on TGF-β1 driven chondrogenesis in collagen sponges. Low concentrations (12.5-25 µg Fe/mL) seem the best compromise to optimize both chondrogenesis and MRI labeling.
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Roeder
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Henrionnet
authors.affiliation: Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé, Centre National de la Recherche Scientifique 5220, Institut National de la Santé et de la Recherche Médicale U1044, Université de Lyon, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Goebel
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gambier
authors.affiliation: Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé, Centre National de la Recherche Scientifique 5220, Institut National de la Santé et de la Recherche Médicale U1044, Université de Lyon, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Beuf
authors.affiliation: Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé, Centre National de la Recherche Scientifique 5220, Institut National de la Santé et de la Recherche Médicale U1044, Université de Lyon, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Grenier
authors.affiliation: Imagerie Adaptative Diagnostique Interventionelle, Institut National de la Santé et de la Recherche Médicale U947, Vandoeuvre-Lès-Nancy, France.
authors.forename: Bailiang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Imagerie Adaptative Diagnostique Interventionelle, Institut National de la Santé et de la Recherche Médicale U947, Vandoeuvre-Lès-Nancy, France.
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Vuissoz
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gillet
authors.affiliation: Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Pinzano
mesh_terms: D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D024043:Collagen Type II / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D005290:Ferric Compounds; D053773:Transforming Growth Factor beta1; C000499:ferric oxide