Reversing bone loss by directing mesenchymal stem cells to bone

Authors

  • Wei Yao,

    Corresponding author
    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
    • Correspondence: Wei Yao, M.D., Department of Medicine, University of California at Davis Medical Center, Sacramento, California 95817, USA. Telephone: 916-734-0763; Fax: 916-734-4773; e-mail: wei.yao@ucdmc.ucdavis.edu

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  • Min Guan,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Junjing Jia,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Weiwei Dai,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Yu-An E. Lay,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Sarah Amugongo,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Ruiwu Liu,

    1. Department of Biochemistry and Molecular Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • David Olivos,

    1. Department of Biochemistry and Molecular Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Mary Saunders,

    1. Department of Biochemistry and Molecular Medicine, University of California at Davis Medical Center, Sacramento, California, USA
    2. Department of Internal Medicine, Stem Cell Program and Institute for Regenerative Cures, University of California at Davis Medical Center, Sacramento, California, USA
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  • Kit S. Lam,

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
    2. Department of Biochemistry and Molecular Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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  • Jan Nolta,

    1. Department of Internal Medicine, Stem Cell Program and Institute for Regenerative Cures, University of California at Davis Medical Center, Sacramento, California, USA
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  • Diana Olvera,

    1. Department of Materials Science and Engineering, University of California at Berkeley, Berkeley, California, USA
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  • Robert O. Ritchie,

    1. Department of Materials Science and Engineering, University of California at Berkeley, Berkeley, California, USA
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  • Nancy E. Lane

    1. Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California, USA
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Errata

This article is corrected by:

  1. Errata: Erratam: Reversing bone loss by directing mesenchymal stem cells to bone Volume 32, Issue 2, 601, Article first published online: 13 January 2014

  • Author contributions: W. Y.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; M.G.: collection and/or assembly of data, data analysis and interpretation; J.J., W.D., Y.E.L., S.A., R.L., M.S., and D.O.: collection and/or assembly of data, data analysis and interpretation; K.S.L., J.N., R.O.R., and N.E.L.: conception and design, final approval of manuscript.

Abstract

Bone regeneration by systemic transplantation of mesenchymal stem cells (MSCs) is problematic due to the inability to control the MSCs' commitment, growth, and differentiation into functional osteoblasts on the bone surface. Our research group has developed a method to direct the MSCs to the bone surface by conjugating a synthetic peptidomimetic ligand (LLP2A) that has high affinity for activated α4β1 integrin on the MSC surface, with a bisphosphonates (alendronate) that has high affinity for bone (LLP2A-Ale), to direct the transplanted MSCs to bone. Our in vitro experiments demonstrated that mobilization of LLP2A-Ale to hydroxyapatite accelerated MSC migration that was associated with an increase in the phosphorylation of Akt kinase and osteoblastogenesis. LLP2A-Ale increased the homing of the transplanted MSCs to bone as well as the osteoblast surface, significantly increased the rate of bone formation and restored both trabecular and cortical bone loss induced by estrogen deficiency or advanced age in mice. These results support LLP2A-Ale as a novel therapeutic option to direct the transplanted MSCs to bone for the treatment of established bone loss related to hormone deficiency and aging. Stem Cells 2013;31:2003-2014

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