Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic activity

Stem cells have been successfully used for the treatment of critical limb ischemia (CLI). We conducted a clinical trial to determine the feasibility of using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the treatment of CLI. Unexpectedly, two diabetic patients developed peripheral microthrombosis. This adverse effect, which contrasts with the reported antithrombotic properties of MSCs, may stem from the diabetic environment that alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of developing thrombosis. Here, we confirm this premise by demonstrating that diabetic AdMSCs cultured in the presence of blood sera expressed and released higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue plasminogen activator, and lower D-dimer formation compared with nondiabetic AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we recommend including new preclinical safety tests, such as the D-dimer and/or the tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio tests, to assess fibrinolytic activity of cells before implantation. © 2013 by the American Diabetes Association.The authors are supported by the Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía (Grant PI- 0022/2008) and Consejería de Innovación Ciencia y Empresa, Junta de Andalucía (Grant CTS-6505, INP-2011-1615-900000). Fondo Europeo de Desarrollo Regional (FEDER) cofunded grants from Instituto de Salud Carlos III (Red TerCel-Grant RD06/0010/0025, PI10/00964, and PI10/00871) and the Ministry of Health and Consumer Affairs (Advanced Therapies Program Grant TRA-120). Support from Fundación de la Sociedad Española de Diabetes (FSED) and Fundación Andaluza de Investigación y Desarrollo (FAID) allow access to databanks.Peer Reviewe

Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic activity.

Journal Article; Research Support, Non-U.S. Gov't;Stem cells have been successfully used for the treatment of critical limb ischemia (CLI). We conducted a clinical trial to determine the feasibility of using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the treatment of CLI. Unexpectedly, two diabetic patients developed peripheral microthrombosis. This adverse effect, which contrasts with the reported antithrombotic properties of MSCs, may stem from the diabetic environment that alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of developing thrombosis. Here, we confirm this premise by demonstrating that diabetic AdMSCs cultured in the presence of blood sera expressed and released higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue plasminogen activator, and lower d-dimer formation compared with nondiabetic AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we recommend including new preclinical safety tests, such as the d-dimer and/or the tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio tests, to assess fibrinolytic activity of cells before implantation.The authors are supported by the Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía (Grant PI-0022/2008) and Consejería de Innovación Ciencia y Empresa, Junta de Andalucía (Grant CTS-6505, INP-2011-1615-900000). Fondo Europeo de Desarrollo Regional (FEDER) cofunded grants from Instituto de Salud Carlos III (Red TerCel-Grant RD06/0010/0025, PI10/00964, and PI10/00871) and the Ministry of Health and Consumer Affairs (Advanced Therapies Program Grant TRA-120).Ye