title: In-vivo comparison of the acute retention of stem cell derivatives and fibroblasts after intramyocardial transplantation in the mouse model.
abstract: OBJECTIVE
  Various strategies have been applied to increase the engraftment of an intramyocardial cell transplant (Tx) to treat ischemic myocardium. Thereby, co-transplanted fibroblasts (FB) improve the long-term survival of stem cell derivatives (SCD) in a murine model of myocardial infarction. For therapeutic use, the time frame in which FB exert putative supportive effects needs to be identified. Therefore, we tracked the biodistribution and retention of SCD and FB in vivo using highly sensitive positron emission tomography (PET) imaging.
  
  
  METHODS
  Murine [(18)F]-fluorodeoxyglucose (FDG) labeled SCD and FB were transplanted after left anterior descending artery (LAD) ligation into the border zone of the ischemic area in female C57BL/6 mice. Cardiac retention and biodistribution during the initial 2 h after injection were measured via PET imaging.
  
  
  RESULTS
  Massive initial cell loss occurred independently of the cell type. Thereby, FB were retained slightly, yet significantly better than SCD until 60 min post-injection (7.5 ± 1.7 vs. 5.2 ± 0.7% ID at 25 min and 7.0 ± 1.5 vs. 4.8 ± 0.8% ID at 60 min). Thereafter, a fraction of ∼ 5% that withstood the massive initial washout remained at the site of injection independently of the applied cell type (120 min, SCD vs. FB P = 0.64). Most of the lost cells were detected in the lungs (∼ 30 % ID).
  
  
  CONCLUSIONS
  We were able to quantitatively define the retention and biodistribution of different cell types via PET imaging in a mouse model after intramyocardial Tx. The utmost accuracy was achieved through this cell- and organ-specific approach by correcting PET data for cellular FDG efflux. Thereby, we observed a massive initial cell loss of ∼ 95%, causing low rates of long-term engraftment for both SCD and FB. We conclude that FB are not privileged compared to SCD regarding their acute retention kinetics, and therefore exert their beneficial effects at a later time point.
authors: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, Germany.
authors: Cajetan
authors: C
authors: Lang
authors: Sebastian
authors: S
authors: Lehner
authors: Andrei
authors: A
authors: Todica
authors: Guido
authors: G
authors: Boening
authors: Mathias
authors: M
authors: Zacherl
authors: Wolfgang-Michael
authors: WM
authors: Franz
authors: Bernd Joachim
authors: BJ
authors: Krause
authors: Peter
authors: P
authors: Bartenstein
authors: Marcus
authors: M
authors: Hacker
authors: Robert
authors: R
authors: David
mesh_terms: D000818:Animals; D002470:Cell Survival; D053595:Embryonic Stem Cells / Q000000981:diagnostic imaging / Q000637:transplantation*; D005260:Female; D005347:Fibroblasts / Q000000981:diagnostic imaging / Q000637:transplantation*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000628:therapy*; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D019788:Fluorodeoxyglucose F18