title: Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.
abstract: While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.
authors.affiliation: 1 Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden .|2 Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universtätsmedizin Berlin , Berlin, Germany .|3 Department of Nephrology and Intensive Care Medicine, Charité Universtätsmedizin Berlin , Berlin, Germany .
authors.forename: Guido
authors.initials: G
authors.lastname: Moll
authors.affiliation: 4 Department of Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: Lech
authors.initials: L
authors.lastname: Ignatowicz
authors.affiliation: 3 Department of Nephrology and Intensive Care Medicine, Charité Universtätsmedizin Berlin , Berlin, Germany .
authors.forename: Rusan
authors.initials: R
authors.lastname: Catar
authors.affiliation: 3 Department of Nephrology and Intensive Care Medicine, Charité Universtätsmedizin Berlin , Berlin, Germany .
authors.forename: Christian
authors.initials: C
authors.lastname: Luecht
authors.affiliation: 1 Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden .|5 Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge , Stockholm, Sweden .
authors.forename: Behnam
authors.initials: B
authors.lastname: Sadeghi
authors.affiliation: 6 Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University , Stockholm, Sweden .
authors.forename: Osama
authors.initials: O
authors.lastname: Hamad
authors.affiliation: 7 Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet , Stockholm, Sweden .|8 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University , Heidelberg, Germany .
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.affiliation: 2 Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universtätsmedizin Berlin , Berlin, Germany .|3 Department of Nephrology and Intensive Care Medicine, Charité Universtätsmedizin Berlin , Berlin, Germany .
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.affiliation: 4 Department of Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
authors.affiliation: 1 Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet , Stockholm, Sweden .|5 Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge , Stockholm, Sweden .
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000628:therapy; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006493:Heparin; D003577:Cytochrome P-450 Enzyme System; D013925:Thromboplastin; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase