Nonintegrating Knockdown and Customized Scaffold Design Enhances Human Adipose-Derived Stem Cells in Skeletal Repair§

Authors

  • Benjamin Levi,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Jeong S. Hyun,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Emily R. Nelson,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Shuli Li,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Daniel T. Montoro,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Derrick C. Wan,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Fang Jun Jia,

    1. Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, California, USA
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  • Jason C. Glotzbach,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Aaron W. James,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
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  • Min Lee,

    1. Division of Advanced Prosthodontics, Biomaterials, and Hospital Dentistry, University of California Los Angeles School of Dentistry, Los Angeles, California, USA
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  • Mei Huang,

    1. Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, California, USA
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  • Natalina Quarto,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
    2. Dipartimento di Scienze Chirurgiche, Anestesiologiche-Rianimatorie e dell'mergenza “Giuseppe Zannini,” Universita' degli Studi di Napoli Federico II, Napoli, Italy
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  • Geoffrey C. Gurtner,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
    2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA
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  • Joseph C. Wu,

    1. Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, California, USA
    2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA
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  • Michael T. Longaker

    Corresponding author
    1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery DivisionStanford University School of Medicine, Stanford, California, USA
    2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA
    • Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California 94305-5148, USA
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    • Telephone: 650-736-1707; Fax: 650-736-1705


  • Author contributions: B.L. and D.C.W.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; E.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; S.L., J.S.H., F.J., M.H., and J.P.G.: collection and/or assembly of data and data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; D.T.M.: collection and/or assembly of data; M.L.: provision of study material or patients; N.Q.: conception and design, administrative support, collection and/or assembly of data, and data analysis and interpretation; G.C.G., J.C.W. and M.T.L.: conception and design and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS October 13, 2011.

Abstract

An urgent need exists in clinical medicine for suitable alternatives to available techniques for bone tissue repair. Human adipose-derived stem cells (hASCs) represent a readily available, autogenous cell source with well-documented in vivo osteogenic potential. In this article, we manipulated Noggin expression levels in hASCs using lentiviral and nonintegrating minicircle short hairpin ribonucleic acid (shRNA) methodologies in vitro and in vivo to enhance hASC osteogenesis. Human ASCs with Noggin knockdown showed significantly increased bone morphogenetic protein (BMP) signaling and osteogenic differentiation both in vitro and in vivo, and when placed onto a BMP-releasing scaffold embedded with lentiviral Noggin shRNA particles, hASCs more rapidly healed mouse calvarial defects. This study therefore suggests that genetic targeting of hASCs combined with custom scaffold design can optimize hASCs for skeletal regenerative medicine. STEM Cells 2011;29:2018–2029.

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