High frequency of cephalic neural crest cells shows coexistence of neurogenic, melanogenic, and osteogenic differentiation capacities

Centre National de la Recherche Scientifique Unité Propre de Recherche 2197 Laboratoire Développement, Evolution et Plasticité du Système Nerveux, Institut de Neurobiologie Alfred Fessard, 91198 Gif-sur-Yvette, France.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2009; 106(22):8947-52. DOI: 10.1073/pnas.0903780106
Source: PubMed


The neural crest (NC) is a vertebrate innovation that distinguishes vertebrates from other chordates and was critical for the development and evolution of a "New Head and Brain." In early vertebrates, the NC was the source of dermal armor of fossil jawless fish. In extant vertebrates, including mammals, the NC forms the peripheral nervous system, melanocytes, and the cartilage and bone of the face. Here, we show that in avian embryos, a large majority of cephalic NC cells (CNCCs) have the ability to differentiate into cell types as diverse as neurons, melanocytes, osteocytes, and chondrocytes. Moreover, we find that the morphogen Sonic hedgehog (Shh) acts on CNCCs to increase endochondral osteogenesis while having no effect on osteoblasts prone to membranous ossification. We have developed culture conditions that demonstrate that "neural-mesenchymal" differentiation abilities are present in more than 90% of CNCCs. A highly multipotent progenitor (able to yield neurons, glia, melanocytes, myofibroblasts, chondrocytes, and osteocytes) comprises 7-13% of the clonogenic cells in the absence and presence of Shh, respectively. This progenitor is a good candidate for a cephalic NC stem cell.

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Available from: Giordano Wosgrau Calloni
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    • "Especially in context of bone regeneration under contribution of autologously transplanted stem cells, directed differentiation of human NCSCs into an osteogenic lineage has gained great interest. Usually, the in vitro-osteogenesis by cranial NCSCs is induced by supplementation of the cultivation medium with a cocktail of (bio-) chemical agents including the synthetic glucocorticoid dexamethasone (Baek et al., 2013; Calloni et al., 2009). Importantly, in vivo, dexamethasone exhibits severe side effects common to other glucocorticoids including immunosuppressant action, which could increase the risk of infection after autologous transplantation of NCSCs. "
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    ABSTRACT: Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in context of bone regeneration. Ideally, exogenously differentiation should mimic endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and membranes with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.
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    • "derivatives including neurons, glia, melanocytes, smooth muscle cells (SMCs), chondrocytes, and osteoblasts [11] [12]. Therefore, these neural crest cells have been termed " neural crest stem cells " (NCSCs). "
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    • "Efforts were made to identify multipotent neural crest stem cells of cephalic origin that have capacities to differentiate into neuron, melanocytes, chondrocytes, and osteocytes by genetic fate mapping (Calloni et al. 2009). The cranial neural crest forms ectomesenchyme that is characterized by the ability to differentiate into numerous cell types normally associated with mesoderm, including muscle and bone (Le Lievre and Le Douarin 1975; Le Douarin et al. 1998). "
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