Letter by Kaye and Esler Regarding Article “Extracardiac Progenitor Cells Repopulate Most Major Cell Types in the Transplanted Human Heart”
To the Editor:
We read with interest the recent study by Minami et al.1 Using the male-female cardiac transplant chimera paradigm, Minami and colleagues recently reported on the potential for repopulation of the transplanted heart by extracardiac progenitor cells. In that study, the authors describe observations regarding the appearance of Y-chromosome–positive cells that were positive for the nonspecific neuronal marker S100. This finding leads the investigators to conclude that they have provided structural evidence for cardiac reinnervation.
The phenomenon of cardiac reinnervation has been extensively studied over the past decade.2–5 These investigations consistently reported that the process of reinnervation, as reflected by functional and biochemical measures, is time dependent and typically not detectable at <2 years after transplantation. The study by Minami et al1 provides no information regarding the time course of the appearance of the S100-, Y-chromosome–positive cells, nor does it report the exact location of these cells within the myocardium. Previous studies suggest that the process of reinnervation occurs in a heterogeneous manner, though in a base-to-apex pattern.3 This pattern of reinnervation has been taken to indicate that the process relies on the influx of new neurons rather than on the deposition of extracardiac progenitors as suggested by Minami et al.1 This suggestion is also inconsistent with physiological data that demonstrate that physical stress increases the rate of norepinephrine release from the intermediate-term transplanted heart.2 This finding may imply that sympathetic neurons in the transplanted heart are under central control. Accordingly, the relevance and exact identity of the S100-, Y-positive cells described in the study by Minami et al are of interest, but their role remains uncertain.
Minami E, Laflamme MA, Saffitz JE, Murry CE. Extracardiac progenitor cells repopulate most major cell types in the transplanted human heart. Circulation. 2005; 112: 2951–2958.
Kaye DM, Esler M, Kingwell B, McPherson G, Esmore D, Jennings G. Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans. Circulation. 1993; 88: 1110–1118.
Bengel FM, Ueberfuhr P, Ziegler SI, Nekolla S, Reichart B, Schwaiger M. Serial assessment of sympathetic reinnervation after orthotopic heart transplantation: a longitudinal study using PET and C-11 hydroxyephedrine. Circulation. 1999; 99: 1866–1871.