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In-vivo comparison of the acute retention of stem cell derivatives and fibroblasts after intramyocardial transplantation in the mouse model.

Abstract：

PURPOSE: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.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Lang C,Lehner S,Todica A,Boening G,Zacherl M,Franz WM,Krause BJ,Bartenstein P,Hacker M,David R

doi

10.1007/s00259-014-2858-8

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

2325-36

issue

eissn

1619-7070

issn

1619-7089

journal_volume

pub_type

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In-vivo comparison of the acute retention of stem cell derivatives and fibroblasts after intramyocardial transplantation in the mouse model.