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.
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.
Authors: Nobuhisa Ohno; Paul W M Fedak; Richard D Weisel; Masashi Komeda; Donald A G Mickle; Ren-Ke Li Journal: Jpn J Thorac Cardiovasc Surg Date: 2002-11
Authors: P Meneton; M Bloch-Faure; A A Hagege; H Ruetten; W Huang; S Bergaya; D Ceiler; D Gehring; I Martins; G Salmon; C M Boulanger; J Nussberger; B Crozatier; J M Gasc; D Heudes; P Bruneval; T Doetschman; J Ménard; F Alhenc-Gelas Journal: Proc Natl Acad Sci U S A Date: 2001-02-20 Impact factor: 11.205
Authors: Yerem Yeghiazarians; Yan Zhang; Megha Prasad; Henry Shih; Shereen A Saini; Junya Takagawa; Richard E Sievers; Maelene L Wong; Neel K Kapasi; Rachel Mirsky; Juha Koskenvuo; Petros Minasi; Jianqin Ye; Mohan N Viswanathan; Franca S Angeli; Andrew J Boyle; Matthew L Springer; William Grossman Journal: Mol Ther Date: 2009-04-21 Impact factor: 11.454