title: Successful chondrogenesis within scaffolds, using magnetic stem cell confinement and bioreactor maturation.
abstract: Tissue engineering strategies, such as cellularized scaffolds approaches, have been explored for cartilage replacement. The challenge, however, remains to produce a cartilaginous tissue incorporating functional chondrocytes and being large and thick enough to be compatible with the replacement of articular defects. Here, we achieved unprecedented cartilage tissue production into a porous polysaccharide scaffold by combining of efficient magnetic condensation of mesenchymal stem cells, and dynamic maturation in a bioreactor. In optimal conditions, all the hallmarks of chondrogenesis were enhanced with a 50-fold increase in collagen II expression compared to negative control, an overexpression of aggrecan and collagen XI, and a very low expression of collagen I and RUNX2. Histological staining showed a large number of cellular aggregates, as well as an increased proteoglycan synthesis by chondrocytes. Interestingly, electron microscopy showed larger chondrocytes and a more abundant extracellular matrix. In addition, the periodicity of the neosynthesized collagen fibers matched that of collagen II. These results represent a major step forward in replacement tissue for cartilage defects.
  
  
  
  A combination of several innovative technologies (magnetic cell seeding, polysaccharide porous scaffolds, and dynamic maturation in bioreactor) enabled unprecedented successful chondrogenesis within scaffolds.
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057 CNRS & University Paris Diderot, Paris F-75205 Cedex 13, France. Electronic address: nathalie.luciani@univ-paris-diderot.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Luciani
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057 CNRS & University Paris Diderot, Paris F-75205 Cedex 13, France.
authors.forename: Vicard
authors.initials: V
authors.lastname: Du
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057 CNRS & University Paris Diderot, Paris F-75205 Cedex 13, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Gazeau
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057 CNRS & University Paris Diderot, Paris F-75205 Cedex 13, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Richert
authors.affiliation: Laboratoire de recherche vasculaire translationnelle, INSERM UMR 1148 & University Paris Diderot, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
authors.affiliation: INSERM, U791, LIOAD, Nantes F-44042, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Visage
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057 CNRS & University Paris Diderot, Paris F-75205 Cedex 13, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Wilhelm
mesh_terms: D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D005786:Gene Expression Regulation; D006801:Humans; D060526:Magnetic Fields; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016062:Porosity; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Bioreactor; Cartilage defect; Chondrogenesis; Magnetic mesenchymal stem cells; Tissue engineering