title: The contribution of stem cell therapy to skeletal muscle remodeling in heart failure.
abstract: BACKGROUND
  The aim of our study was to investigate whether stem cell (SC) therapy with human amniotic fluid stem cells (hAFS, fetal stem cells) and rat adipose tissue stromal vascular fraction cells-GFP positive cells (rSVC-GFP) was able to produce favorable effects on skeletal muscle (SM) remodeling in a well-established rat model of right heart failure (RHF).
  
  
  METHODS
  RHF was induced by monocrotaline (MCT) in Sprague-Dawley rats. Three weeks later, four millions of hAFS or rSVC-GFP cells were injected via tail vein. SM remodeling was assessed by Soleus muscle fiber cross sectional area (CSA), myocyte apoptosis, myosin heavy chain (MHC) composition, satellite cells pattern, and SC immunohistochemistry.
  
  
  RESULTS
  hAFS and rSVC-GFP injection produced significant SC homing in Soleus (0.68 ± 1.0 and 0.67 ± 0.75% respectively), with a 50% differentiation toward smooth muscle and endothelial cells. Pro-inflammatory cytokines were down regulated to levels similar to those of controls. SC-treated (SCT) rats showed increased CSA (p<0.004 vs MCT) similarly to controls with a reshift toward the slow MHC1 isoform. Apoptosis was significantly decreased (11.12.± 8.8 cells/mm(3) hAFS and 13.1+7.6 rSVC-GFP) (p<0.001 vs MCT) and similar to controls (5.38 ± 3.0 cells/mm(3)). RHF rats showed a dramatic reduction of satellite cells(MCT 0.2 ± 0.06% Pax7 native vs controls 2.60 ± 2.46%, p<0.001), while SCT induced a repopulation of both native and SC derived satellite cells (p<0.005).
  
  
  CONCLUSIONS
  SC treatment led to SM remodeling with satellite cell repopulation, decreased atrophy and apoptosis. Modulation of the cytokine milieu might play a crucial pathophysiological role with a possible scenario for autologous transplantation of SC in pts with CHF myopathy.
authors: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors: Chiara
authors: C
authors: Castellani
authors: Giorgio
authors: G
authors: Vescovo
authors: Barbara
authors: B
authors: Ravara
authors: Chiara
authors: C
authors: Franzin
authors: Michela
authors: M
authors: Pozzobon
authors: Regina
authors: R
authors: Tavano
authors: Luisa
authors: L
authors: Gorza
authors: Emanuele
authors: E
authors: Papini
authors: Roberto
authors: R
authors: Vettor
authors: Paolo
authors: P
authors: De Coppi
authors: Gaetano
authors: G
authors: Thiene
authors: Annalisa
authors: A
authors: Angelini
mesh_terms: D000650:Amnion / Q000166:cytology / Q000637:transplantation; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006333:Heart Failure / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D016207:Cytokines
keywords: Cytokines; Heart failure; Monocrotaline; Satellite cells; Skeletal muscle; Stem cells