Can Cellular Transplantation Improve Function in Doxorubicin-Induced Heart Failure?

Scorsin, Marcio MD
Hagege, Albert A. MD
Dolizy, Isabelle MD
Marotte, Francoise FS
Mirochnik, Nicolas MD
Copin, Henri MD
Barnoux, Muriel MD
le Bert, Marc PhD
Samuel, Jane-Lise PhD
Rappaport, Lydie PhD
Menasche, Philippe MD, PhD

From the Department of Cardiovascular Surgery, INSERM U-127 and Cytogenetics Laboratory, Hopital Lariboisiere; INSERM U-114 College de France; and the Research in Imaging Laboratory, Faculte de Medecine Necker-Enfants Malades, Paris, France.
Correspondence to Dr Philippe Menasche, Department of Cardiovascular Surgery, Hopital Lariboisiere, 2, rue Ambroise Pare, 75475 Paris Cedex 10, France.

Circulation 98(19S):p 151II-155II, November 10, 1998.

Background

Transplantation of fetal cardiomyocytes has been shown to improve function of regionally infarcted myocardium, but its effects on global heart failure are still unknown.

Methods and Results-Heart failure was induced in female mice by intraperitoneal injection of doxorubicin (2 mg/kg twice per week over 2 cycles of 2 weeks separated by a 2-week drug-free period). One week after the end of treatment, left ventricular function was assessed by transthoracic echocardiography (baseline). Animals were then randomized into 3 groups: The treated group (n=12) received an intramyocardial injection of fetal cardiomyocytes (1x10⁶ in 10 [micro sign]L) harvested from transgenic mice expressing the gene of beta-galactosidase, the control group (n=15) received an equivalent volume of culture medium alone, and 10 sham mice had no surgery. Two weeks and 1 month after transplantation, function was again assessed echocardiographically. At baseline, fractional shortening was not significantly different between the 3 groups. It then significantly increased in cell-treated mice at 2 weeks and 1 month after transplantation (P<0.002 and P<0.03 versus baseline, respectively), whereas it did not change in untreated animals. Transplanted cells could not be identified by beta-galactosidase activity or presence of Y chromosome (with 1 exception).

Conclusions

Cellular transplantation can improve function of globally failing hearts by a mechanism that might not necessarily involve the sustained presence of transplanted cells but rather the effects of cardioprotective factors released by them. (Circulation. 1998;98:II-151-II-156.)