title: Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy.
abstract: BACKGROUND
  Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy.
  
  
  METHODS
  We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography.
  
  
  RESULTS
  Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left-ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05).
  
  
  CONCLUSIONS
  These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Arman T
authors.initials: AT
authors.lastname: Askari
authors.forename: Samuel
authors.initials: S
authors.lastname: Unzek
authors.forename: Zoran B
authors.initials: ZB
authors.lastname: Popovic
authors.forename: Corey K
authors.initials: CK
authors.lastname: Goldman
authors.forename: Farhad
authors.initials: F
authors.lastname: Forudi
authors.forename: Matthew
authors.initials: M
authors.lastname: Kiedrowski
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Rovner
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: James D
authors.initials: JD
authors.lastname: Thomas
authors.forename: Paul E
authors.initials: PE
authors.lastname: DiCorleto
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000601:surgery*; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim