Acosta, LourdesHmadcha, AbdelkrimEscacena, NataliaPérez-Camacho, Inmaculadade la Cuesta, AntonioRuiz-Salmeron, RafaelGauthier, Benoit RSoria, Bernat2016-07-132016-07-132013-12Acosta L, Hmadcha A, Escacena N, Pérez-Camacho I, de la Cuesta A, Ruiz-Salmeron R, et al. Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic activity. Diabetes. 2013; 62(12):4266-90012-1797http://hdl.handle.net/10668/2263Journal 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.enTissue Plasminogen ActivatorPlasminogen Activator Inhibitor 1Células del Estroma MesenquimatosoDiabetes Mellitus, Type 2FibrinólisisMedical Subject Headings::Named Groups::Persons::Age Groups::AdolescentMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and overMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Blood Physiological Phenomena::Blood Physiological Processes::Hemostasis::Blood Coagulation::FibrinolysisMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal CellsMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Plasminogen Inactivators::Plasminogen Activator Inhibitor 1Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Tissue Plasminogen ActivatorMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissueresearch article24043757open access10.2337/db13-08961939-327XPMC3837061