title: Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy.
abstract: BACKGROUND
  Cell transplantation is a promising therapy for treating end-stage heart failure. Bone marrow mononuclear cells (BMMNC) have been used to enhance angiogenesis in ischemic heart disease. However, the effect of BMMNC transplantation in non-ischemic dilated cardiomyopathy is unknown. In this study, we evaluated the efficacy of BMMNC transplantation in doxorubicin-induced cardiomyopathy in a rat model.
  
  
  METHODS
  Doxorubicin (15 mg/kg, IP) was introduced into 52 Lewis rats. They were divided into 3 groups at 4 weeks after injection: transplant group (TX, BMMNC [1 x 10(6)] implantation, n = 18), control group (CN, saline injection, n = 18), and sham group (SH, thoracotomy, n = 16). At 4 weeks after surgery, we used echocardiography to measure systolic left ventricular diameter (LVDs), diastolic left ventricular diameter (LVDd), fractional shortening (FS), and left ventricular wall thickness/LVDs. We used a Langendorff apparatus to measure systolic, diastolic, and developed pressures. We used radioimmunoassay to measure circulating atrial natriuretic peptide concentration, and we performed histologic study, including electron-microscopic study.
  
  
  RESULTS
  Left ventricular wall thickness/LVDs in the TX group was the largest of all groups (p < 0.05). Systolic and developed pressures in the TX group were the greatest (p < 0.005). Systolic left ventricular diameter, FS, and end-diastolic pressure in the TX group were smaller than in the SH group (p < 0.05). These cardiac parameters did not differ significantly between TX and CN groups, but secondary changes (decreased heart weight, developed ascites, and increased atrial natriuretic peptide concentration) caused by doxorubicin-induced heart failure were most attenuated in the TX group. In the TX group, vascular density was greatest (p < 0.05) in the left ventricular free wall and in the septum. In addition, electron microscopy showed that myocardium in the TX group was most maintained.
  
  
  CONCLUSIONS
  Bone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Ishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Tomita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Masaki
authors.initials: M
authors.lastname: Hamamoto
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohtsu
authors.forename: Michiharu
authors.initials: M
authors.lastname: Suga
authors.forename: Chikao
authors.initials: C
authors.lastname: Yutani
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Yagihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D016026:Bone Marrow Transplantation; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004317:Doxorubicin; D006334:Heart Function Tests; D006339:Heart Rate; D008297:Male; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D017725:Ventricular Pressure
chemical_list: D004317:Doxorubicin; D009320:Atrial Natriuretic Factor