title: Engineering Small-Scale and Scaffold-Based Bone Organs via Endochondral Ossification Using Adult Progenitor Cells.
abstract: Bone development, growth, and repair predominantly occur through the process of endochondral ossification, characterized by remodelling of cartilaginous templates. The same route efficiently supports engineering of bone marrow as a niche for hematopoietic stem cells (HSC). Here we describe a combined in vitro/in vivo system based on bone marrow-derived Mesenchymal Stem/Stromal Cells (MSC) that duplicates the hallmark cellular and molecular events of endochondral ossification during development. The model requires MSC culture with instructive molecules to generate hypertrophic cartilage tissues. The resulting constructs complete the endochondral route upon in vivo implantation, in the timeframe of up to 12 weeks. The described protocol is clearly distinct from the direct ossification approach typically used to drive MSC towards osteogenesis. Recapitulation of endochondral ossification allows modelling of stromal-HSC interactions in physiology and pathology and allows engineering processes underlying bone regeneration.
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.|IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: Scotti
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tonnarelli
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Adam
authors.initials: A
authors.lastname: Papadimitropoulos
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Elia
authors.initials: E
authors.lastname: Piccinini
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Atanas
authors.initials: A
authors.lastname: Todorov
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Centola
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
authors.affiliation: Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. ivan.martin@usb.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D016025:Bone Transplantation; D002356:Cartilage / Q000166:cytology*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D000070631:Diastasis, Bone; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010012:Osteogenesis; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
keywords: Bone regeneration; Endochondral ossification; Hematopoietic stem cells; Mesenchymal stem cells; Osteogenesis; Scaffold