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

作者：Choudhury Tawfiq; Mozid Abdul; Hamshere Steve; Yeo Chia; Pellaton Cyril; Arnous Samer; Saunders Natalie; Brookman Pat; Jain Ajay; Locca Didier; Archbold Andrew; Knight Charles; Wragg Andrew; Davies Ceri; Mills Peter; Parmar Mahesh; Rothman Martin; Choudry Fizzah; Jones Daniel A; Agrawal Samir; Martin John; Mathur Anthony^*

来源：European Journal of Heart Failure, 2017, 19(1): 138-147.

DOI：10.1002/ejhf.676

• Bone marrow-derived cells
• Ischaemic cardiomyopathy
• Granulocyte colony-stimulating factor

Aims 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.
Methods and results 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.
Conclusion 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.

• 出版日期2017-1