Characterization of endothelial-like cells derived from human mesenchymal stem cells

Authors

  • J. W. LIU,

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
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  • S. DUNOYER-GEINDRE,

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
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  • V. SERRE-BEINIER,

    1. Surgical Research Unit, Department of Surgery, University, Hospital of Geneva, Geneva, Switzerland
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    • 1These authors contributed equally to this manuscript.

  • G. MAI,

    1. Surgical Research Unit, Department of Surgery, University, Hospital of Geneva, Geneva, Switzerland
    2. Institute of Digestive Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
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    • 1These authors contributed equally to this manuscript.

  • J.-F. LAMBERT,

    1. Division of Hematology, Department of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland
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  • R. J. FISH,

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
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  • G. PERNOD,

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
    2. Hemostasis unit DBPC, CHU Grenoble, France
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  • L. BUEHLER,

    1. Division of Hematology, Department of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland
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  • H. BOUNAMEAUX,

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
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  • E. K. O. KRUITHOF

    1. Division of Angiology and Hemostasis, University Hospital of Geneva, Department of Internal Medicine, University Hospital of Geneva, Geneva
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Egbert K. O. Kruithof, Division of Angiology and Hemostasis, University Hospital of Geneva, CH-1211 Geneva, Switzerland.
Tel.: +41 22 3729758; fax: +41 22 3729299; e-mail: egbert.kruithof@hcuge.ch

Abstract

Summary.  Background:  Blood-derived endothelial progenitor cells (EPC) have been used to treat ischemic disease. However, the number of EPC that can be obtained from adult blood is limited.

Objective:  To characterize endothelial-like cells obtained from human bone marrow and determine their ability to stimulate new blood vessel formation in vivo.

Methods:  Mononuclear cells (MNC) were isolated from human bone marrow or umbilical cord blood and cultured in endothelial growth medium (EGM-2). Mesenchymal stem cells (MSC) were isolated from bone marrow and induced to differentiate into endothelial-like cells (MSCE), or adipocytes or osteocytes by growth in EGM-2, adipogenic or osteogenic medium.

Results:  Cells obtained by culturing bone marrow MNC in EGM-2 formed cord- or tube-like structures when grown on MatrigelTM and expressed several endothelial marker proteins. However, cell morphology and the profile of endothelial marker protein expression were different from those of cord blood-derived EPC (cbEPC). Cells with a similar phenotype were obtained by differentiation of MSC into MSCE, which was accompanied by an increase of endothelial marker proteins and a diminished capacity to differentiate into adipocytes. Subcutaneous implantation of MSCE in collagen plugs in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice resulted in formation of functional blood vessels that had incorporated the MSCE.

Conclusions:  Our results show that MSCE and cbEPC are different cell types. The formation of functional blood vessels by MSCE, combined with high yields and a reduced capacity to differentiate into other cell types compared with MSC, makes these cells potentially useful for autologous therapy of ischemic disease.

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