Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial).
OBJECTIVE
Regenerative treatment with mesenchymal stromal cells (MSCs) has been promising in patients with ischaemic heart failure but needs confirmation in larger randomized trials. We aimed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure.


RESULTS
The MSC-HF trial is a randomized, double-blind, placebo-controlled trial. Patients were randomized 2 : 1 to intra-myocardial injections of MSC or placebo, respectively. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography at 6 months follow-up. Sixty patients aged 30-80 years with severe ischaemic heart failure, New York Heart Association (NYHA) classes II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Fifty-five patients completed the 6-month follow-up (37 MSCs vs. 18 placebo). At 6 months, LVESV was reduced in the MSC group: -7.6 (95% CI -11.8 to -3.4) mL (P = 0.001), and increased in the placebo group: 5.4 (95% CI -0.4 to 11.2) mL (P = 0.07). The difference between groups was 13.0 (95% CI 5.9-20.1) mL (P = 0.001). Compared with placebo, there were also significant improvements in LVEF of 6.2% (P<0.0001), stroke volume of 18.4 mL (P < 0.0001), and myocardial mass of 5.7 g (P = 0.001). No differences were found in NYHA class, 6-min walking test and Kansas City cardiomyopathy questionnaire. No side effects were identified.


CONCLUSIONS
Intra-myocardial injections of autologous culture expanded MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure.


BACKGROUND
NCT00644410 (ClinicalTrials.gov).
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark abbe@dadlnet.dk.
Anders Bruun
AB
Mathiasen
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Abbas Ali
AA
Qayyum
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Erik
E
Jørgensen
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Steffen
S
Helqvist
Department of Clinical Immunology 2034, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Anne
A
Fischer-Nielsen
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark Department of Radiology, Diagnostic Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Klaus F
KF
Kofoed
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Mandana
M
Haack-Sørensen
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Annette
A
Ekblond
Cardiac Catheterization Laboratory 2014 and Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
Jens
J
Kastrup
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057791:Cardiac Imaging Techniques / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D015552:Injections, Intralesional; D018810:Magnetic Resonance Angiography; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D011788:Quality of Life; D014057:Tomography, X-Ray Computed
Clinical trial; Heart failure; Ischaemic heart disease; Mesenchymal stromal cell; Stem cell