title: Autotransplantation of mesenchymal stromal cells from bone-marrow to heart in patients with severe stable coronary artery disease and refractory angina--final 3-year follow-up.
abstract: BACKGROUND
  The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (BMMSCs) in patients with severe stable coronary artery disease (CAD) and refractory angina.
  
  
  METHODS
  Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous BMMSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. BMMSCs were injected into an ischemic, viable region of the myocardium. Patients were followed for 3 years.
  
  
  RESULTS
  We found significant clinical improvements in exercise time (p=0.0016), angina class (CCS) (p<0.0001), weekly number of angina attacks (p<0.0001) and use of nitroglycerine from (p=0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p<0.0001). When comparing all hospital admissions from 3 years before to 3 years after treatment, we observed highly reduced admission rates for stable angina (p<0.0001), revascularization (p=0.003) and overall cardiovascular disease (p<0.0001). No early or late side-effects of the treatment were observed.
  
  
  CONCLUSIONS
  The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs, in patients with severe CAD and refractory angina, demonstrated sustained clinical effects, reduced hospital admissions for cardiovascular disease and excellent long-term safety. The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression.
authors.affiliation: Cardiac Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Cardiac Catheterization Laboratory 2014, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: abbe@dadlnet.dk.
authors.forename: Anders Bruun
authors.initials: AB
authors.lastname: Mathiasen
authors.forename: Mandana
authors.initials: M
authors.lastname: Haack-Sørensen
authors.forename: Erik
authors.initials: E
authors.lastname: Jørgensen
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000628:therapy*; D016026:Bone Marrow Transplantation; D003324:Coronary Artery Disease / Q000628:therapy*; D005080:Exercise Test; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy; D009206:Myocardium / Q000166:cytology*; D010359:Patient Readmission; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: Angiogenesis; Chronic myocardial ischemia; Mesenchymal stromal cell; Refractory angina; Stem cell; Stem cell therapy