Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype
DOI: 10.1016/j.biomaterials.2011.07.049
Title: Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype
Journal Title: Biomaterials
Volume: 32
Issue: 32
Publication Date: November 2011
Start Page: 8182
End Page: 8189
Published online: online 11 August 2011
ISSN: 0142-9612
Affiliations:

  • a Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

  • b Department of Biologic and Materials Sciences, The University of Michigan, 1011 North University Ave., Room 2211, Ann Arbor, MI 48109-1078, United States

  • c Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States

  • d Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, United States

  • e Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, United States
  • Abstract: pulposus grafts are needed for patients requiring replacement of their degenerated intervertebral discs. Bone marrow-derived mesenchymal stem cells (MSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. One of the key issues of constructing functional nucleus pulposus using MSCs, however, is to differentiate MSCs into nucleus pulposus phenotype invitro and to maintain their phenotypic stability invivo. In this study, three-dimensional (3D) nanofibrous poly(l-lactide) (PLLA) scaffolds were seeded with multi-potent rabbit MSCs and the constructs were induced along nucleus pulposus development routes in a hypoxia chamber (2% O2) in the presence of TGF-β1. It was found that nanofibrous scaffold could support the differentiation of rabbit MSCs towards a nucleus pulposus-like phenotype invitro, as evidenced by upregulated expression of a few important nucleus pulposus-associated genes (aggrecan, type II collagen and Sox-9), abundant deposition of extracellular matrix (glycosaminoglycan (GAG) and type II collagen), and the continuous expression of the nucleus pulposus-specific marker, hypoxia-inducible factor (HIF)-1α. The subcutaneous implantation results confirmed that hypoxic induction before implantation could help the constructs to retain their phenotype and resist calcification invivo. Therefore, the above data showed the promise of using 3D nanofibrous scaffolds in combination with TGF-β1 and hypoxic induction to regenerate functional nucleus pulposus grafts for intervertebral disc replacement.
    Accepted: 16 July 2011
    Received: 17 May 2011
    Keywords: Rabbit bone marrow-derived mesenchymal stem cell; Nanofiber; Porous scaffold; Hypoxia; Nucleus pulposus graft
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