TGF-β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward <i>Nucleus Pulposus</i>-like Cells
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- Pauline Colombier
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Johann Clouet
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Cécile Boyer
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Maëva Ruel
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Gaëlle Bonin
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Julie Lesoeur
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Anne Moreau
- Université de Nantes, UFR Médecine, Nantes, France
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- Borhane-Hakim Fellah
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Pierre Weiss
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Laurent Lescaudron
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Anne Camus
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
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- Jérôme Guicheux
- INSERM UMRS 791, Laboratoire d'Ingénierie Osteo Articulaire et Dentaire (LIOAD), Nantes, France
説明
<jats:title>Abstract</jats:title> <jats:p>Degenerative disc disease (DDD) primarily affects the central part of the intervertebral disc namely the nucleus pulposus (NP). DDD explains about 40% of low back pain and is characterized by massive cellular alterations that ultimately result in the disappearance of resident NP cells. Thus, repopulating the NP with regenerative cells is a promising therapeutic approach and remains a great challenge. The objectives of this study were to evaluate the potential of growth factor-driven protocols to commit human adipose stromal cells (hASCs) toward NP-like cell phenotype and the involvement of Smad proteins in this differentiation process. Here, we demonstrate that the transforming growth factor-β1 and the growth differentiation factor 5 synergistically drive the nucleopulpogenic differentiation process. The commitment of the hASCs was robust and highly specific as attested by the expression of NP-related genes characteristic of young healthy human NP cells. In addition, the engineered NP-like cells secreted an abundant aggrecan and type II collagen rich extracellular matrix comparable with that of native NP. Furthermore, we demonstrate that these in vitro engineered cells survived, maintained their specialized phenotype and secretory activity after in vivo transplantation in nude mice subcutis. Finally, we provide evidence suggesting that the Smad 2/3 pathway mainly governed the acquisition of the NP cell molecular identity while the Smad1/5/8 pathway controlled the NP cell morphology. This study offers valuable insights for the development of biologically-inspired treatments for DDD by generating adapted and exhaustively characterized autologous regenerative cells.</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 34 (3), 653-667, 2015-12-18
Oxford University Press (OUP)
