Response to Letter Regarding Article, “Direct Intramyocardial but Not Intracoronary Injection of Bone Marrow Cells Induces Ventricular Arrhythmias in a Rat Chronic Ischemic Heart Failure Model”
We thank Dr Ly for his interest in our article.1 We, too, strongly believe that cell therapy as a treatment for heart failure requires further laboratory research to ensure its future success.
It is likely that not only the injection site, but also the number and volume of injections and the number of cells injected, will influence therapeutic benefit and arrhythmogenicity after intramyocardial cell injection.2 Although this is an important clinical point, its illustration in small animal models has obvious limitations; large animal or human studies are needed. Dr Ly’s assertion that skeletal myoblasts are too large to be injected via an intracoronary route may not be right. We have demonstrated previously that both antegrade and retrograde intracoronary injections of skeletal myoblasts are effective for treating heart disease.3,4
We do not aim to insist that retrograde intracoronary injection is superior to antegrade infusion. However, it is a fact that transendothelial migration of donor cells injected via antegrade intracoronary injection is seriously limited. Our data (K.S., S.F., A.V-C., S.R.C., K.Y., L.E.F., J.L., P.J.R.B., C.M.N.T. M.Y., unpublished data, 2006) showed that over 80% of bone marrow cells injected via antegrade intracoronary injection simply passed through the heart and were immediately flushed out. Retrograde intracoronary injection, which might address this problem, is feasible, as it has already been applied in patients.
In our article,1 we noted that intramyocardial injection induced a local inflammatory response that was associated with arrhythmia occurrence, whereas little inflammation and rare arrhythmia were observed after retrograde intracoronary injection. We agree that the paracrine effect plays an important role in the mechanism of cell therapy–induced benefits. So far, we have not observed clear differences between intracoronary and intramyocardial injections in the expression of paracrine mediators. We will continue to investigate further details of the paracrine effect.
Fukushima S, Varela-Carver A, Coppen SR, Yamahara K, Felkin LE, Lee J, Barton PJ, Terracciano CM, Yacoub MH, Suzuki K. Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation. 2007; 115: 2254–2261.
Ott HC, Kroess R, Bonaros N, Marksteiner R, Margreiter E, Schachner T, Laufer G, Hering S. Intramyocardial microdepot injection increases the efficacy of skeletal myoblast transplantation. Eur J Cardiothorac Surg. 2005; 27: 1017–1021.