Utilizzo di cellule progenitrici derivate dal midollo osseo

Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute Myocardial Infarction
New Engl J Med 2006; 355:1199-209 - Abstract - Diapositive
Intracoronary Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction
New Engl J Med 2006; 355:1210-21 - Abstract - Diapositive
Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction
New Engl J Med 2006; 355:1122-32 - Abstract - Diapositive

Commento:
Nel New England Journal Medicine del 21 settembre di quest'anno sono stati pubblicati tre lavori con risultati discordanti riguardanti la capacità di cellule progenitrici derivate dal midollo osseo di correggere l'out come in seguito a infarto del miocardio.
Tutti e tre gli studi provengono da gruppi europei sottolineando che, al momento, c'è un piccolo vantaggio competitivo riguardo agli Stati Uniti in quest'area.
Purtroppo i risultati non sono concordanti. Si passa da uno studio che in generale può essere considerato positivo ad uno studio negativo.
Perché queste differenze? Ci sono tante possibili spiegazioni. Ritengo, comunque, che la più importante sia la qualità delle cellule isolate e come siano state conservate prima della iniezione. Sappiamo che non tutte le cellule che vengono isolate dal midollo osseo con le tecniche utilizzate sono cellule che saranno poi in grado di "riparare" il danno. Sappiamo anche che queste cellule sono molto delicate nel loro bilancio e ce richiedono attenzioni particolari. Penso proprio che stiamo assistendo ad una fase di medicina "eroica" nella quale non conosciamo ancora con cosa stiamo lavorando ma riteniamo che in questo modo si possa ottenere un beneficio per il paziente.
Fino a quando non saranno approfonditi i discorsi di comparare e spiegare le differenze tra gli studi e verificare perché in alcuni casi queste cellule hanno un effetto ed altri no rimarremo sempre in sospeso nel giudizio e continueremo a dimostrare la nostra scarsa conoscenza di meccanismi che sono alla base del lavoro che si è svolto. Quindi è evidente che è necessario un grande sforzo per approfondire lavori sperimentali di comprensione prima di ritornare a pensare di iniettare queste cellule in persone che hanno avuto un infarto anche perché la sicurezza di questo approccio rimane tutto da verificare in tempi medio lunghi.

Alberico L. Catapano, Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano

Abstract:

Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute Myocardial Infarction
Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K.
New Engl J Med 2006; 355:1199-209 - Diapositive

BACKGROUND: Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment.
METHODS: Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size.
RESULTS: Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events.
CONCLUSIONS: With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.

Intracoronary Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction
Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators.
New Engl J Med 2006; 355:1210-21 - Diapositive

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction.
METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy.
RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01).
CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.


Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction
Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM.
New Engl J Med 2006; 355:1122-32- Diapositive

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction.
METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy.
RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01).
CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.