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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.
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2, Adult, Male, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over, Adolescent, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Plasminogen Inactivators::Plasminogen Activator Inhibitor 1, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult, Plasminogen Activator Inhibitor 1, Humans, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Tissue Plasminogen Activator, Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue, Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged, Original Research, Aged, Aged, 80 and over, Fibrinolysis, Medical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Blood Physiological Phenomena::Blood Physiological Processes::Hemostasis::Blood Coagulation::Fibrinolysis, Medical Subject Headings::Check Tags::Female, Mesenchymal Stem Cells, Middle Aged, Medical Subject Headings::Check Tags::Male, Adipose Tissue, Diabetes Mellitus, Type 2, Tissue Plasminogen Activator, Female, Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal Cells
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2, Adult, Male, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over, Adolescent, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Plasminogen Inactivators::Plasminogen Activator Inhibitor 1, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult, Plasminogen Activator Inhibitor 1, Humans, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Tissue Plasminogen Activator, Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue, Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged, Original Research, Aged, Aged, 80 and over, Fibrinolysis, Medical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Blood Physiological Phenomena::Blood Physiological Processes::Hemostasis::Blood Coagulation::Fibrinolysis, Medical Subject Headings::Check Tags::Female, Mesenchymal Stem Cells, Middle Aged, Medical Subject Headings::Check Tags::Male, Adipose Tissue, Diabetes Mellitus, Type 2, Tissue Plasminogen Activator, Female, Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal Cells
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