Bone Marrow Mononuclear Cells Have Neurovascular Tropism and Improve Diabetic Neuropathy

Authors

  • Hyongbum Kim,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Jong-seon Park,

    1. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Yong Jin Choi,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Mee-Ohk Kim,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Yang Hoon Huh,

    1. Boston Biomedical Research Institute, Watertown, Massachusetts, USA
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  • Sung-Whan Kim,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Ji Woong Han,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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  • JiYoon Lee,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Sinae Kim,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Mackenzie A. Houge,

    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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  • Masaaki Ii,

    1. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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  • Young-sup Yoon

    Corresponding author
    1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    2. Division of Cardiovascular Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
    • Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB 3009, Atlanta, GA 30322, USA
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    • Telephone: 404-727-8176; Fax: 404-727-3988


  • Author contributions: H.K.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; J.S.P.: conception and design, collection and/or assembly of data, data analysis and interpretation; Y.J.C.: collection and/or assembly of data, contributing experimentation, administrative support; M.O.K.: manuscript writing, final approval of manuscript; Y.H.H.: collection and/or assembly of data; S.W.K.: collection and/or assembly of data; J.W.H.: collection and/or assembly of data; J.Y.L.: collection and/or assembly of data, contributing experimentation, administrative support; S.K.: contributing experimentation; M.A.H.: contributing experimentation; M.I.: contributing experimentation; Y.S.Y.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS April 9, 2009.

Abstract

Bone marrow-derived mononuclear cells (BMNCs) have been shown to effectively treat ischemic cardiovascular diseases. Because diabetic neuropathy (DN) is causally associated with impaired angiogenesis and deficiency of angiogenic and neurotrophic factors in the nerves, we investigated whether DN can be ameliorated by local injection of BMNCs. Severe peripheral neuropathy, characterized by a significant decrease in the motor and sensory nerve conduction velocities (NCVs), developed 12 weeks after the induction of diabetes with streptozotocin in rats. The injection of BMNCs restored motor and sensory NCVs to normal levels and significantly improved vascular density and blood flow in diabetic nerves over 4 weeks. Fluorescent microscopic observation revealed that DiI-labeled BMNCs preferentially engrafted in sciatic nerves. Whole-mount fluorescent imaging and confocal microscopic evaluation demonstrated that many of the BMNCs localized following the course of the vasa nervorum in close proximity to blood vessels without incorporation into vasa nervorum as endothelial cells at a detectable level. Real-time reverse transcription-polymerase chain reaction analysis showed that the levels of angiogenic and neurotrophic factors were significantly increased in the nerves by BMNC injection. Local transplantation of BMNCs improved experimental DN by augmenting angiogenesis and increasing angiogenic and neurotrophic factors in peripheral nerves. These findings suggest that BMNC transplantation may represent a novel therapeutic option for treating DN. STEM CELLS 2009;27:1686–1696

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