title: Bone marrow-derived mononuclear cell therapy alleviates left ventricular remodeling and improves heart function in rat-dilated cardiomyopathy.
abstract: OBJECTIVE
  This study hypothesized that bone marrow-derived mononuclear cell (BMDMNC) therapy may improve cardiac function through preventing cell death, alleviating left ventricular (LV) remodeling, and enhancing angio-/vasculo-genesis, as well as preserving LV contractility in a rat model of dilated cardiomyopathy (DCM).
  
  
  METHODS
  A model of DCM in Sprague-Dawley rats was used to investigate the effects of BMDMNC therapy on inflammatory and oxidative response, energy depression, cellular apoptosis, expressions of protein kinase C-(PKC)-epsilon, and connexin43 protein (Cx43) in LV myocardium and heart function.
  
  
  METHODS
  An animal model research laboratory at Kaohsiung Chang Gung Memorial Hospital.
  
  
  METHODS
  The rats were divided into group 1 (normal control, n = 8), group 2 (saline-treated DCM, n = 10), and group 3 (1.2 x 10 BMDMNC implanted into LV anterior wall on day 35 after DCM induction, n = 10). The DCM and normal control rats were killed on day 90 following DCM induction.
  
  
  RESULTS
  The results demonstrated that Cx43 protein expression and messenger RNA expressions of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, endothelial nitric oxide synthase, and interleukin-10 were higher, whereas messenger RNA expressions of endothelin-1 and matrix metalloproteinase-9 were lower in groups 1 and 3 than in group 2 (all p < 0.05). Additionally, expressions of PKC-epsilon in plasma membrane and mitochondria and LV function were conserved in group 1 and improved in group 3, whereas cardiomyocyte apoptosis, mitochondrial oxidative stress, and fibrosis of LV myocardium were reduced in groups 1 and 3 than in group 2 (all p < 0.005).
  
  
  CONCLUSIONS
  BMDMNC therapy in DCM significantly improves LV function by limiting cellular apoptosis, inflammatory and oxidative responses, and by up-regulating expressions of Cx43, PKC-epsilon, and energy transcription factors.
authors.affiliation: Division of General Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Republic of China.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Chiang-Hua
authors.initials: CH
authors.lastname: Chiang
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Chiung-Jen
authors.initials: CJ
authors.lastname: Wu
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Morgan
authors.initials: M
authors.lastname: Fu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling