Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.
OBJECTIVE
Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms.


RESULTS
Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior.


CONCLUSIONS
Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection.


BACKGROUND
This trial was registered at http://www.clinicaltrials.gov under NCT00462774.
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Boris A
BA
Nasseri
Pediatric Bone Marrow Transplant Program, Charité, Universitätsmedizin Berlin, Berlin 10117, Germany.
Wolfram
W
Ebell
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Michael
M
Dandel
Department of Anesthesiology, Deutsches Herzzentrum Berlin, Berlin 13353, Germany.
Marian
M
Kukucka
Department of Internal Medicine/Cardiology, Deutsches Herzzentrum Berlin, Berlin 13353, Germany.
Rolf
R
Gebker
Department of Internal Medicine/Cardiology, Deutsches Herzzentrum Berlin, Berlin 13353, Germany.
Adelina
A
Doltra
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Christoph
C
Knosalla
Berlin-Brandenburg Center for Regenerative Therapies, Berlin 13353, Germany.
Yeong-Hoon
YH
Choi
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany.
Roland
R
Hetzer
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin 13353, Germany Berlin-Brandenburg Center for Regenerative Therapies, Berlin 13353, Germany stamm@dhzb.de.
Christof
C
Stamm
D000071916:AC133 Antigen; D015703:Antigens, CD; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D001026:Coronary Artery Bypass / Q000379:methods* / Q000401:mortality; D005260:Female; D006023:Glycoproteins; D006321:Heart / Q000502:physiology*; D006801:Humans; D015552:Injections, Intralesional; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000401:mortality / Q000628:therapy*; D010455:Peptides; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000628:therapy
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
Bypass; Cells; Impaired LV function; Infarction; Ischaemic heart disease