naa a22 4500 510739202 CHVBK 20180411083022.0 cr unu---uuuuu 180411e20130601xx s 000 0 eng 10.1007/s12015-013-9433-8 doi (NATIONALLICENCE)springer-10.1007/s12015-013-9433-8 Mesenchymal Stem Cells as a Treatment for Peripheral Arterial Disease: Current Status and Potential Impact of Type II Diabetes on Their Therapeutic Efficacy [Elektronische Daten] [Jinglian Yan, Guodong Tie, Ting Xu, Katharine Cecchini, Louis Messina] 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. Springer Science+Business Media New York, 2013 Mesenchymal stem cells nationallicence Peripheral arterial disease nationallicence Oxidative stress nationallicence Limb ischemia nationallicence (A) : Autologous nationallicence (Al) : Allogenic nationallicence ABI : Ankle-brachial index nationallicence AE : Adverse events nationallicence AFS : Amputation-free survival nationallicence CLI : Critical limb ischemia nationallicence CL : Contralateral leg nationallicence DSA : Digital subtraction angiography nationallicence MRA : Magnetic resonance angiography nationallicence PS : Perfusion scintigraphy nationallicence QoL : Quality of life survey nationallicence RP : Rest pain nationallicence TAO : Thromboangiitis obliterans nationallicence TcPO2 : Transcutaneous oxygen pressure nationallicence TTF : Time to treatment failure nationallicence WH : Wound healing nationallicence WT/D : Pain free walking time/distance nationallicence Yan Jinglian Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut Tie Guodong Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut Xu Ting Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut Cecchini Katharine Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut Messina Louis Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut Stem Cell Reviews and Reports Humana Press Inc 9/3(2013-06-01), 360-372 1550-8943 9:3<360 2013 9 12015 https://doi.org/10.1007/s12015-013-9433-8 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12015-013-9433-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yan Jinglian Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut NATIONALLICENCE 700 1- Tie Guodong Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut NATIONALLICENCE 700 1- Xu Ting Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut NATIONALLICENCE 700 1- Cecchini Katharine Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut NATIONALLICENCE 700 1- Messina Louis Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, 01655, Worcester, MA, USA aut NATIONALLICENCE 773 0- Stem Cell Reviews and Reports Humana Press Inc 9/3(2013-06-01), 360-372 1550-8943 9:3<360 2013 9 12015 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer