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

dc.contributor.authorAcosta, Lourdes
dc.contributor.authorHmadcha, Abdelkrim
dc.contributor.authorEscacena, Natalia
dc.contributor.authorPérez-Camacho, Inmaculada
dc.contributor.authorde la Cuesta, Antonio
dc.contributor.authorRuiz-Salmeron, Rafael
dc.contributor.authorGauthier, Benoit R
dc.contributor.authorSoria, Bernat
dc.contributor.authoraffiliation[Acosta,L; Hmadcha,A; Escacena,N; Gauthier,BR; Soria,B] Centro Andaluz de Biología Molecular y Medicina Regenerativa, Sevilla, Spain. [Hmadcha,A; Soria,B] CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain. [Pérez-Camacho, I; de la Cuesta,A; Ruiz-Salmeron,R] Hospitales Universitarios San Lázaro and Virgen Macarena, Sevilla, Spaines
dc.contributor.funderThe 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).
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractStem 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
dc.identifier.citationAcosta 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):4266-9es
dc.publisherAmerican Diabetes Associationes
dc.rights.accessRightsopen access
dc.subjectTissue Plasminogen Activatores
dc.subjectPlasminogen Activator Inhibitor 1es
dc.subjectCélulas del Estroma Mesenquimatosoes
dc.subjectDiabetes Mellitus, Type 2es
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adultes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Agedes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and overes
dc.subject.meshMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2es
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Blood Physiological Phenomena::Blood Physiological Processes::Hemostasis::Blood Coagulation::Fibrinolysises
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Check Tags::Malees
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal Cellses
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Agedes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Plasminogen Inactivators::Plasminogen Activator Inhibitor 1es
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::Tissue Plasminogen Activatores
dc.subject.meshMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissuees
dc.titleAdipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic
dc.typeresearch article
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