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.
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.
Authors: R David; C Brenner; J Stieber; F Schwarz; S Brunner; M Vollmer; E Mentele; J Müller-Höcker; S Kitajima; H Lickert; R Rupp; W-M Franz Journal: Nat Cell Biol Date: 2008-02-24 Impact factor: 28.824
Authors: Peter Donndorf; Guenther Kundt; Alexander Kaminski; Can Yerebakan; Andreas Liebold; Gustav Steinhoff; Aenne Glass Journal: J Thorac Cardiovasc Surg Date: 2011-03-03 Impact factor: 5.209
Authors: Katica Stojanov; Erik F J de Vries; Dick Hoekstra; Aren van Waarde; Rudi A J O Dierckx; Inge S Zuhorn Journal: Mol Imaging Date: 2012-02 Impact factor: 4.488
Authors: Wilhelm Roell; Zhong J Lu; Wilhelm Bloch; Sharon Siedner; Klaus Tiemann; Ying Xia; Eva Stoecker; Michaela Fleischmann; Heribert Bohlen; Robert Stehle; Eugen Kolossov; Gottfried Brem; Klaus Addicks; Gabriele Pfitzer; Armin Welz; Juergen Hescheler; Bernd K Fleischmann Journal: Circulation Date: 2002-05-21 Impact factor: 29.690
Authors: John Terrovitis; Riikka Lautamäki; Michael Bonios; James Fox; James M Engles; Jianhua Yu; Michelle K Leppo; Martin G Pomper; Richard L Wahl; Jurgen Seidel; Benjamin M Tsui; Frank M Bengel; M Roselle Abraham; Eduardo Marbán Journal: J Am Coll Cardiol Date: 2009-10-20 Impact factor: 24.094
Authors: H Miles Prince; Dominic M Wall; David Ritchie; Dirk Honemann; Simon Harrrison; Hang Quach; Mick Thompson; Rodney Hicks; Eddie Lau; Jill Davison; Maureen Loudovaris; Jude Moloney; Bruce Loveland; Jacques Bartholeyns; Andrew Katsifis; Linda Mileshkin Journal: J Immunother Date: 2008 Feb-Mar Impact factor: 4.456
Authors: Andrea J Mitchell; Eric Sabondjian; Kimberley J Blackwood; Jane Sykes; Lela Deans; Qingping Feng; Robert Z Stodilka; Frank S Prato; Gerald Wisenberg Journal: Int J Cardiovasc Imaging Date: 2012-06-27 Impact factor: 2.357
Authors: Paula Müller; Natalia Voronina; Frauke Hausburg; Cornelia A Lux; Frank Wiekhorst; Gustav Steinhoff; Robert David Journal: Stem Cells Int Date: 2016-10-04 Impact factor: 5.443
Authors: Mark G MacAskill; Adriana S Tavares; Junxi Wu; Christophe Lucatelli; Joanne C Mountford; Andrew H Baker; David E Newby; Patrick W F Hadoke Journal: Sci Rep Date: 2017-03-13 Impact factor: 4.379
Authors: María Collantes; Beatriz Pelacho; María José García-Velloso; Juán José Gavira; Gloria Abizanda; Itziar Palacios; Luis Rodriguez-Borlado; Virginia Álvarez; Elena Prieto; Margarita Ecay; Eduardo Larequi; Iván Peñuelas; Felipe Prósper Journal: J Transl Med Date: 2017-03-13 Impact factor: 5.531
Authors: Mayra Lorena Moreira; Priscylla da Costa Medeiros; Sergio Augusto Lopes de Souza; Bianca Gutfilen; Paulo Henrique Rosado-de-Castro Journal: Stem Cells Int Date: 2016-01-12 Impact factor: 5.443