Can cellular transplantation improve function in doxorubicin-induced heart failure?

Academic Article

Abstract

  • 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 (1 x 10(6) in 10 microL) 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.
  • Published In

  • Circulation  Journal
  • Keywords

  • Animals, Cardiac Output, Low, Cell Transplantation, Doxorubicin, Echocardiography, Female, Fetal Tissue Transplantation, Heart, Mice, Myocardium, Time Factors
  • Pubmed Id

  • 19193585
  • Author List

  • Scorsin M; Hagege AA; Dolizy I; Marotte F; Mirochnik N; Copin H; Barnoux M; le Bert M; Samuel JL; Rappaport L
  • Start Page

  • II151
  • End Page

  • II155
  • Volume

  • 98
  • Issue

  • 19 Suppl