Dura Mater Stimulates Human Adipose-Derived Stromal Cells to Undergo Bone Formation in Mouse Calvarial Defects§

Authors

  • Benjamin Levi,

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

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • Shuli Li,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • Aaron W. James,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • Jeong S. Hyun,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • Daniel T. Montoro,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

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

  • Jason P. Glotzbach,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • George W. Commons,

    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
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    • Author contributions: B.L.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; E.R.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; S.L. and J.S.H.: collection and/or assembly of data, data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.T.M.: collection and/or assembly of data; M.L. and G.W.C.: provision of study material or patients; J.P.G.: collection and assembly of data; M.T.L.: conception and design, final approval of manuscript.

  • Michael T. Longaker

    Corresponding author
    1. Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford 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


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

  • §

    First published online in STEM CELLSEXPRESS June 7, 2011.

Abstract

Human adipose-derived stromal cells (hASCs) have a proven capacity to aid in osseous repair of calvarial defects. However, the bone defect microenvironment necessary for osseous healing is not fully understood. In this study, we postulated that the cell-cell interaction between engrafted ASCs and host dura mater (DM) cells is critical for the healing of calvarial defects. hASCs were engrafted into critical sized calvarial mouse defects. The DM-hASC interaction was manipulated surgically by DM removal or by insertion of a semipermeable or nonpermeable membrane between DM and hASCs. Radiographic, histologic, and gene expression analyses were performed. Next, the hASC-DM interaction is assessed by conditioned media (CM) and coculture assays. Finally, bone morphogenetic protein (BMP) signaling from DM was investigated in vivo using novel BMP-2 and anti-BMP-2/4 slow releasing scaffolds. With intact DM, osseous healing occurs both from host DM and engrafted hASCs. Interference with the DM-hASC interaction dramatically reduced calvarial healing with abrogated BMP-2–Smad-1/5 signaling. Using CM and coculture assays, mouse DM cells stimulated hASC osteogenesis via BMP signaling. Through in vivo manipulation of the BMP-2 pathway, we found that BMP-2 plays an important role in DM stimulation of hASC osteogenesis in the context of calvarial bone healing. BMP-2 supplementation to a defect with disrupted DM allowed for bone formation in a nonhealing defect. DM is an osteogenic cell type that both participates in and stimulates osseous healing in a hASC-engrafted calvarial defect. Furthermore, DM-derived BMP-2 paracrine stimulation appears to play a key role for hASC mediated repair. STEM CELLS 2011;29:1241-1255

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