title: Adult human neural crest-derived cells for articular cartilage repair.
abstract: In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions.
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Karoliina
authors.initials: K
authors.lastname: Pelttari
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pippenger
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Mumme
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Feliciano
authors.affiliation: Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milano, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: Scotti
authors.affiliation: AGINKO Research AG, Route de l'ancienne Papeterie, P. O. Box 30, 1723 Marly, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mainil-Varlet
authors.affiliation: Department of Medicine and Surgery, Federico II Medical School, Via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Procino
authors.affiliation: Musculoskeletal Research Unit, Equine Hospital, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: von Rechenberg
authors.affiliation: Cross-klinik, Bundesstrasse 1, 4009 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwamborn
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jakob
authors.affiliation: Department of Medicine and Surgery, Federico II Medical School, Via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Clemente
authors.initials: C
authors.lastname: Cillo
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. ivan.martin@usb.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
mesh_terms: D000328:Adult; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000473:pathology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006041:Goats; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D009432:Neural Crest / Q000166:cytology* / Q000637:transplantation*; D009473:Neuronal Plasticity; D010865:Pilot Projects; D014182:Transplantation, Autologous; D014945:Wound Healing
chemical_list: D018398:Homeodomain Proteins