Ruiz-Salmeron R.,Hospitales Universitarios San Lazaro and Virgen Macarena |
de la Cuesta-Diaz A.,Hospitales Universitarios San Lazaro and Virgen Macarena |
Constantino-Bermejo M.,Hospitales Universitarios San Lazaro and Virgen Macarena |
Perez-Camacho I.,Hospitales Universitarios San Lazaro and Virgen Macarena |
And 5 more authors.
Cell Transplantation | Year: 2011
Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Subopti-mal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10 6 cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement. © 2011 Cognizant Comm. Corp. Source
Acosta L.,Centro Andaluz Of Biologia Molecular Y Medicina Regenerativa |
Hmadcha A.,Centro Andaluz Of Biologia Molecular Y Medicina Regenerativa |
Hmadcha A.,CIBER ISCIII |
Escacena N.,Centro Andaluz Of Biologia Molecular Y Medicina Regenerativa |
And 6 more authors.
Diabetes | Year: 2013
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. Source