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Sci Transl Med. 2014 Aug 27;6(251):251ra119. doi: 10.1126/scitranslmed.3009688.

Adult human neural crest-derived cells for articular cartilage repair.

Author information

1
Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
2
Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milano, Italy.
3
AGINKO Research AG, Route de l'ancienne Papeterie, P. O. Box 30, 1723 Marly, Switzerland.
4
Department of Medicine and Surgery, Federico II Medical School, Via S. Pansini 5, 80131 Napoli, Italy.
5
Musculoskeletal Research Unit, Equine Hospital, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
6
Cross-klinik, Bundesstrasse 1, 4009 Basel, Switzerland.
7
Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. ivan.martin@usb.ch.

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.

PMID:
25163479
DOI:
10.1126/scitranslmed.3009688
[Indexed for MEDLINE]
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