title: Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium.
abstract: OBJECTIVE
  Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). In this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats.
  
  
  RESULTS
  After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. The impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca(2+)-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy.
  
  
  CONCLUSIONS
  BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists.
authors.affiliation: Dept of Physiological Sciences, Federal University of Espirito Santo, Brazil; Dept of Medicine, Federal University of Sao Paulo, Brazil. Electronic address: leodossantos@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: dos Santos
authors.forename: Giovana A
authors.initials: GA
authors.lastname: Gonçalves
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Davel
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Santos
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Paulo J F
authors.initials: PJ
authors.lastname: Tucci
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D009924:Organ Culture Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: Calcium-handling; Capillary; Hypertrophy; Myocardial remodeling; Stem-cell