title: Retracted: Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.
abstract: c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease.
  
  
  
  In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461.
  
  
  
  This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04).
  
  
  
  These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies.
  
  
  
  University of Louisville Research Foundation and National Institutes of Health.
authors.affiliation: Divisions of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202, USA. rbolli@louisville.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.forename: Atul R
authors.initials: AR
authors.lastname: Chugh
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Amario
authors.forename: John H
authors.initials: JH
authors.lastname: Loughran
authors.forename: Marcus F
authors.initials: MF
authors.lastname: Stoddard
authors.forename: Sohail
authors.initials: S
authors.lastname: Ikram
authors.forename: Garth M
authors.initials: GM
authors.lastname: Beache
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Wagner
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sanada
authors.forename: Julius B
authors.initials: JB
authors.lastname: Elmore
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Donato
authors.initials: D
authors.lastname: Cappetta
authors.forename: Naresh K
authors.initials: NK
authors.lastname: Solankhi
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Fahsah
authors.forename: D Gregg
authors.initials: DG
authors.lastname: Rokosh
authors.forename: Mark S
authors.initials: MS
authors.lastname: Slaughter
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
mesh_terms: D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass / Q000379:methods; D003331:Coronary Vessels; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007269:Injections, Intra-Arterial; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D032383:Myocytes, Cardiac / Q000637:transplantation; D011182:Postoperative Care / Q000379:methods; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D033581:Stem Cell Transplantation / Q000379:methods*; D016019:Survival Analysis; D013997:Time Factors; D020858:Tissue and Organ Harvesting; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology
references.citation: Circ Res. 2011 Apr 1;108(7):857-61
references.pmid: 21330601
references.citation: Circulation. 2009 Nov 24;120(21):2077-87
references.pmid: 19901187
references.citation: J Cardiovasc Magn Reson. 2003 Jul;5(3):505-14
references.pmid: 12882082
references.citation: Nature. 2006 Sep 28;443(7110):404-5
references.pmid: 16957734
references.citation: Br Med Bull. 2011;98:161-85
references.pmid: 21652595
references.citation: Arch Intern Med. 2007 May 28;167(10):989-97
references.pmid: 17533201
references.citation: J Am Coll Cardiol. 2011 Jun 14;57(24):2409-15
references.pmid: 21658561
references.citation: Circ Res. 2008 Jul 3;103(1):107-16
references.pmid: 18556576
references.citation: Eur J Heart Fail. 2010 Jul;12(7):721-9
references.pmid: 20576835
references.citation: J Am Coll Cardiol. 2005 Nov 1;46(9):1651-8
references.pmid: 16256864
references.citation: Circulation. 2010 Jan 19;121(2):293-305
references.pmid: 20048209
references.citation: N Engl J Med. 2006 Sep 21;355(12):1222-32
references.pmid: 16990385
references.citation: Circulation. 2011 Feb 1;123(4):e18-e209
references.pmid: 21160056
references.citation: Am J Cardiol. 2000 Jun 15;85(12):1432-9
references.pmid: 10856388
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14068-73
references.pmid: 17709737
references.citation: J Am Soc Echocardiogr. 1989 Sep-Oct;2(5):358-67
references.pmid: 2698218
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3766-71
references.pmid: 15734798
references.citation: Circ Res. 2011 Jun 10;108(12):1467-81
references.pmid: 21546606
references.citation: Am J Cardiol. 1980 Feb;45(2):210-6
references.pmid: 6965556
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
references.pmid: 15951423
references.citation: JACC Cardiovasc Imaging. 2011 Feb;4(2):150-6
references.pmid: 21329899
references.citation: Neth Heart J. 2009 May;17(5):199-207
references.pmid: 19484156
references.citation: Eur J Heart Fail. 2001 Jun;3(3):315-22
references.pmid: 11378002
references.citation: Eur J Cardiothorac Surg. 2001 Nov;20(5):937-48
references.pmid: 11675178
references.citation: Physiol Rev. 1998 Oct;78(4):1055-85
references.pmid: 9790569
references.citation: Cell. 2003 Sep 19;114(6):763-76
references.pmid: 14505575
references.citation: Physiol Rev. 2008 Apr;88(2):557-79
references.pmid: 18391173