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Eur J Heart Fail ; 19(1): 138-147, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27790824


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.

Transplante de Medula Óssea/métodos , Cardiomiopatias/terapia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco/métodos , Idoso , Cardiomiopatias/sangue , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Vasos Coronários , Feminino , Humanos , Injeções Intra-Arteriais , Injeções Intramusculares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Miocárdio , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Volume Sistólico , Tomografia Computadorizada por Raios X , Transplante Autólogo , Reino Unido
Regen Med ; 9(3): 269-78, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24935040


AIM: This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. METHODS & RESULTS: The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. CONCLUSION: Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.

Transplante de Medula Óssea/métodos , Vias de Administração de Medicamentos , Insuficiência Cardíaca/terapia , Coração , Miocárdio , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Peptídeo Natriurético Encefálico/administração & dosagem , Peptídeo Natriurético Encefálico/farmacologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Projetos Piloto , Transplante Autólogo
Regen Med ; 4(5): 689-96, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19761394


AIMS: Contradictory outcomes from recent clinical trials investigating the transplantation of autologous bone marrow mononuclear cell (BM-MNC) fraction containing stem/progenitor cells to damaged myocardium, following acute myocardial infarction, may be, in part, due to the different cell isolation protocols used. We compared total BM-MNC numbers and its cellular subsets obtained following isolation using Ficoll-Paque and Lymphoprep - two different density gradient media used in the clinical trials. MATERIALS & METHODS: Bone marrow samples were taken from patients entered into the REGENERATE-IHD clinical trial after 5 days of subcutaneous granulocyte colony-stimulating factor injections. Each sample was divided equally for BM-MNC isolation using Ficoll-Paque and Lymphoprep, keeping all other procedural steps constant. Isolated fractions were characterized for hematopoietic stem cells, endothelial progenitor cells, T lymphocytes, B lymphocytes and NK cells using cell surface markers CD34(+), CD133(+)VEGFR2(+), CD45(+)CD3(+), CD45(+)CD19(+) and CD45(+)CD16(+)CD56(+), respectively. There were no significant differences in the absolute numbers and percentage cell recovery of various mononuclear cell types recovered following separation using either density gradient media. Cell viability and the proportion of various cell phenotypes investigated were similar between the two media. They were also equally efficient in excluding unwanted red blood cells, granulocytes and platelets from the final cell products. CONCLUSION: We demonstrated that the composition and quantity of cell types found within therapeutic BM-MNC preparations for use in clinical trials of cardiac stem cell transplantation are not influenced by the type of density gradient media used when comparing Ficoll-Paque and Lymphoprep.

Células da Medula Óssea , Centrifugação com Gradiente de Concentração/métodos , Meios de Cultura , Antígeno AC133 , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Contagem de Células , Sobrevivência Celular , Ensaios Clínicos como Assunto , Citometria de Fluxo , Glicoproteínas/metabolismo , Humanos , Peptídeos/metabolismo , Células-Tronco