X-Ray-Visible Microcapsules Containing Mesenchymal Stem Cells Improve Hind Limb Perfusion in a Rabbit Model of Peripheral Arterial Disease

Authors

  • Dorota A. Kedziorek,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Lawrence V. Hofmann,

    1. Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, California, USA
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  • Yingli Fu,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Wesley D. Gilson,

    1. Siemens Corporation, Corporate Research and Technology, Baltimore, Maryland, USA
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  • Kenyatta M. Cosby,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Bernard Kohl,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Brad P. Barnett,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Brian W. Simons,

    1. Department of Molecular and Comparative Pathobiology,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Piotr Walczak,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Jeff W.M. Bulte,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Kathleen Gabrielson,

    1. Department of Molecular and Comparative Pathobiology,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Dara L. Kraitchman

    Corresponding author
    1. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Molecular and Comparative Pathobiology,Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    • The Johns Hopkins University, Russell H. Morgan Department of Radiology and Radiological Science, 600 N. Wolfe St., 314 Park Building, Baltimore, Maryland 21287, USA
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    • Telephone: 410-955-4892; Fax: 410-614-1977


  • Author contributions: D.A.K.: collection and assembly of data, data analysis, manuscript writing, and final approval of manuscript; L.H. and D.L.K.: conception and design, financial support, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; Y.F. and W.G.: collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; K.C.: Collection and assembly of data, data analysis, and final approval of manuscript; B.K.: administrative support, collection and assembly of data, data analysis, and final approval of manuscript; B.B.: conception and design, manuscript writing, and final approval of manuscript; B.S.: data analysis and interpretation and final approval of manuscript; P.W. and K.G.: data analysis and interpretation, manuscript writing, and final approval of manuscript; J.B.: conception and design, provision of study material, manuscript writing, and final approval of manuscript. D.A.K. and L.V.H. contributed equally to this article.

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

  • First published online in STEM CELLSEXPRESS March 4, 2012.

Abstract

The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC-Xcaps.) In vitro MSC-Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x-ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC-Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast-to-noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC-Xcap-treated animals versus empty Xcaps. Post-mortem immunohistopathology of vessel density by anti-CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap-MSC-treated animals versus empty Xcaps. MSC-Xcaps represent the first x-ray-visible cellular therapeutic with enhanced efficacy for PAD treatment. STEM CELLS2012;30:1286–1296

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