title: Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery.
abstract: OBJECTIVE
  The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET).
  
  
  BACKGROUND
  Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery.
  
  
  METHODS
  The CDCs were derived from syngeneic, male Wistar Kyoto (WK) rats labeled with [(18)F]-fluoro-deoxy-glucose ((18)FDG) and injected intramyocardially into the ischemic region of female WK rats after permanent left coronary artery ligation. The effects of fibrin glue (FG), bradycardia (adenosine), and cardiac arrest were examined. Imaging with (18)FDG PET was performed for quantification of cell retention. Quantitative polymerase chain reaction (PCR) for the male-specific SRY gene was performed to validate the PET results.
  
  
  RESULTS
  Myocardial retention of cells suspended in phosphate-buffered saline 1 h after delivery was 17.6 +/- 11.5% by PCR and 17.8 +/- 7.3% by PET. When CDCs were injected immediately after induction of cardiac arrest, retention was increased to 75.6 +/- 18.6%. Adenosine slowed the ventricular rate and doubled CDC retention (35.4 +/- 5.3%). A similar increase in CDC retention was observed after epicardial application of FG at the injection site (37.5 +/- 8.2%). The PCR revealed a significant increase in 3-week cell engraftment in the FG animals (22.1 +/- 18.6% and 5.3 +/- 3.1%, for FG and phosphate-buffered saline, respectively).
  
  
  CONCLUSIONS
  In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with FG or lowering ventricular rate by adenosine might be clinically translatable methods for improving stem cell engraftment in a beating heart.
authors.affiliation: The Heart Institute, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: John
authors.initials: J
authors.lastname: Terrovitis
authors.forename: Riikka
authors.initials: R
authors.lastname: Lautamäki
authors.forename: Michael
authors.initials: M
authors.lastname: Bonios
authors.forename: James
authors.initials: J
authors.lastname: Fox
authors.forename: James M
authors.initials: JM
authors.lastname: Engles
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Leppo
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Tsui
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
authors.forename: M Roselle
authors.initials: MR
authors.lastname: Abraham
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D002470:Cell Survival; D003331:Coronary Vessels / Q000601:surgery; D005260:Female; D006321:Heart / Q000502:physiology*; D008026:Ligation; D008297:Male; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000637:transplantation*; D049268:Positron-Emission Tomography; D051381:Rats; D011921:Rats, Inbred WKY; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*