Authors: Cajetan Lang Sebastian Lehner Andrei Todica Guido Boening Mathias Zacherl WolfgangMichael Franz Bernd Joachim Krause Peter Bartenstein Marcus Hacker Robert David
Publish Date: 2014/07/26
Volume: 41, Issue: 12, Pages: 2325-2336
Abstract
Various strategies have been applied to increase the engraftment of an intramyocardial cell transplant Tx to treat ischemic myocardium Thereby cotransplanted fibroblasts FB improve the longterm 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 imagingMurine 18 Ffluorodeoxyglucose 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 imagingMassive initial cell loss occurred independently of the cell type Thereby FB were retained slightly yet significantly better than SCD until 60 min postinjection 75 ± 17 vs 52 ± 07 ID at 25 min and 70 ± 15 vs 48 ± 08 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 = 064 Most of the lost cells were detected in the lungs ∼30 IDWe 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 organspecific approach by correcting PET data for cellular FDG efflux Thereby we observed a massive initial cell loss of ∼95 causing low rates of longterm 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
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