Mesenchymal Stem Cells as a Treatment for Peripheral Arterial Disease: Current Status and Potential Impact of Type II Diabetes on Their Therapeutic Efficacy
UMass Chan Affiliations
Department of SurgeryDocument Type
Journal ArticlePublication Date
2013-06-01Keywords
Mesenchymal stem cellsPeripheral arterial disease
Oxidative stress
Limb ischemia
Cardiovascular Diseases
Cell Biology
Endocrinology, Diabetes, and Metabolism
Surgery
Surgical Procedures, Operative
Therapeutics
Metadata
Show full item recordAbstract
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 siteDOI
10.1007/s12015-013-9433-8Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29204PubMed ID
23475434Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1007/s12015-013-9433-8