title: Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina: one-year follow-up.
abstract: In patients with stable coronary artery disease (CAD) and refractory angina, we performed direct intramyocardial injections of autologous mesenchymal stromal cells (MSC) and followed the safety and efficacy of the treatment for 12 months. A total of 31 patients with stable CAD, moderate to severe angina, normal left ventricular ejection fraction, and no further revascularization options were included. Bone marrow MSCs were isolated and culture expanded for 6-8 weeks and then stimulated with vascular endothelial growth factor (VEGF) for 1 week. The 12-month follow-up demonstrated that it was safe to culture expand MSCs and use the cells for clinical treatment. The patients' maximal metabolic equivalent (MET) during exercise increased from 4.23 MET at baseline to 4.72 MET at 12-month follow-up (p < 0.001), Canadian Cardiovascular Society Class (CCS) was reduced from 3.0 to 0.8 (p < 0.001), angina attacks per week from 13.8 to 3.2 (p < 0.001), and nitroglycerin consumption from 10.7 to 3.4 per week (p < 0.001). In addition, Seattle Angina Questionnaire (SAQ) evaluations demonstrated highly significant improvements in physical limitation, angina stability, angina frequency, and quality of life (p < 0.001 for all). It is safe in the intermediate/long term to treat patients with stable CAD using autologous culture expanded MSCs. Previously reported, early and highly significant improvements in exercise capacity and clinical symptoms persist after 12 months. The results are encouraging, and a larger controlled study is warranted.
authors.affiliation: Cardiac Stem Cell Laboratory and Catheterization Laboratory, The Hearth Centre, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Mandana
authors.initials: M
authors.lastname: Haack-Sørensen
authors.forename: Tina
authors.initials: T
authors.lastname: Friis
authors.forename: Anders B
authors.initials: AB
authors.lastname: Mathiasen
authors.forename: Erik
authors.initials: E
authors.lastname: Jørgensen
authors.forename: Louise
authors.initials: L
authors.lastname: Hansen
authors.forename: Ebbe
authors.initials: E
authors.lastname: Dickmeiss
authors.forename: Annette
authors.initials: A
authors.lastname: Ekblond
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000150:complications / Q000628:therapy*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000150:complications / Q000628:therapy*; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008875:Middle Aged; D005996:Nitroglycerin / Q000378:metabolism; D011446:Prospective Studies; D011788:Quality of Life; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D005996:Nitroglycerin