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    Mesenchymal Stem Cells as a Treatment for Peripheral Arterial Disease: Current Status and Potential Impact of Type II Diabetes on Their Therapeutic Efficacy

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    Authors
    Yan, Jinglian
    Tie, Guodong
    Xu, Ting Yu
    Cecchini, Katharine
    Messina, Louis M.
    UMass Chan Affiliations
    Department of Surgery
    Document Type
    Journal Article
    Publication Date
    2013-06-01
    Keywords
    Mesenchymal stem cells
    Peripheral arterial disease
    Oxidative stress
    Limb ischemia
    Cardiovascular Diseases
    Cell Biology
    Endocrinology, Diabetes, and Metabolism
    Surgery
    Surgical Procedures, Operative
    Therapeutics
    
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    Link to Full Text
    http://dx.doi.org/10.1007/s12015-013-9433-8
    Abstract
    Mesenchymal stem cells (MSCs), due to their paracrine, transdifferentiation, and immunosuppressive effects, hold great promise as a therapy for peripheral arterial disease. Diabetes is an important risk factor for peripheral arterial disease; however, little is known of how type II diabetes affects the therapeutic function of MSCs. This review summarizes the current status of preclinical and clinical studies that have been performed to determine the efficacy of MSCs in the treatment of peripheral arterial disease. We also present findings from our laboratory regarding the impact of type II diabetes on the therapeutic efficacy of MSCs neovascularization after the induction of hindlimb ischemia. In our studies, we documented that experimental type II diabetes in db/db mice impaired MSCs' therapeutic function by favoring their differentiation towards adipocytes, while limiting their differentiation towards endothelial cells. Moreover, type II diabetes impaired the capacity of MSCs to promote neovascularization in the ischemic hindlimb. We further showed that these impairments of MSC function and multipotency were secondary to hyperinsulinemia-induced, Nox4-dependent oxidant stress in db/db MSCs. Should human MSCs display similar oxidant stress-induced impairment of function, these findings might permit greater leverage of the potential of MSC transplantation, particularly in the setting of diabetes or other cardiovascular risk factors, as well as provide a therapeutic approach by reversing the oxidant stress of MSCs prior to transplantation.
    Source
    Stem Cell Rev. 2013 Jun;9(3):360-72. doi: 10.1007/s12015-013-9433-8. Link to article on publisher's site
    DOI
    10.1007/s12015-013-9433-8
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29204
    PubMed ID
    23475434
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1007/s12015-013-9433-8
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