title: An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.
abstract: The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function.
  
  
  
  Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons.
  
  
  
  We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Tawfiq
authors: T
authors: Choudhury
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Abdul
authors: A
authors: Mozid
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Steve
authors: S
authors: Hamshere
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Chia
authors: C
authors: Yeo
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Cyril
authors: C
authors: Pellaton
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Samer
authors: S
authors: Arnous
authors: Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK.
authors: Natalie
authors: N
authors: Saunders
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Pat
authors: P
authors: Brookman
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Ajay
authors: A
authors: Jain
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Didier
authors: D
authors: Locca
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Andrew
authors: A
authors: Archbold
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Charles
authors: C
authors: Knight
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Andrew
authors: A
authors: Wragg
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Ceri
authors: C
authors: Davies
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Peter
authors: P
authors: Mills
authors: MRC Clinical Trials Unit, London, UK.
authors: Mahesh
authors: M
authors: Parmar
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Martin
authors: M
authors: Rothman
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Fizzah
authors: F
authors: Choudry
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Daniel A
authors: DA
authors: Jones
authors: Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK.
authors: Samir
authors: S
authors: Agrawal
authors: British Heart Foundation Laboratories, Department of Medicine, University College London, London, UK.
authors: John
authors: J
authors: Martin
authors: Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors: Anthony
authors: A
authors: Mathur
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D003331:Coronary Vessels; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007269:Injections, Intra-Arterial; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D006113:United Kingdom
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D016179:Granulocyte Colony-Stimulating Factor
keywords: Bone marrow-derived cells; Granulocyte colony-stimulating factor; Ischaemic cardiomyopathy