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Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold

BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the effi...

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Autores principales: Nakamuta, Juliana S., Danoviz, Maria E., Marques, Fabio L. N., dos Santos, Leonardo, Becker, Claudia, Gonçalves, Giovana A., Vassallo, Paula F., Schettert, Isolmar T., Tucci, Paulo J. F., Krieger, Jose E.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695782/
https://www.ncbi.nlm.nih.gov/pubmed/19547700
http://dx.doi.org/10.1371/journal.pone.0006005
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author Nakamuta, Juliana S.
Danoviz, Maria E.
Marques, Fabio L. N.
dos Santos, Leonardo
Becker, Claudia
Gonçalves, Giovana A.
Vassallo, Paula F.
Schettert, Isolmar T.
Tucci, Paulo J. F.
Krieger, Jose E.
author_facet Nakamuta, Juliana S.
Danoviz, Maria E.
Marques, Fabio L. N.
dos Santos, Leonardo
Becker, Claudia
Gonçalves, Giovana A.
Vassallo, Paula F.
Schettert, Isolmar T.
Tucci, Paulo J. F.
Krieger, Jose E.
author_sort Nakamuta, Juliana S.
collection PubMed
description BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function. METHODOLOGY/PRINCIPAL FINDINGS: (99m)Tc-labeled BMC (6×10(6) cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV(+)) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by γ-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. CONCLUSIONS/SIGNIFICANCE: These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches.
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spelling pubmed-26957822009-06-23 Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold Nakamuta, Juliana S. Danoviz, Maria E. Marques, Fabio L. N. dos Santos, Leonardo Becker, Claudia Gonçalves, Giovana A. Vassallo, Paula F. Schettert, Isolmar T. Tucci, Paulo J. F. Krieger, Jose E. PLoS One Research Article BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function. METHODOLOGY/PRINCIPAL FINDINGS: (99m)Tc-labeled BMC (6×10(6) cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV(+)) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by γ-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. CONCLUSIONS/SIGNIFICANCE: These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches. Public Library of Science 2009-06-23 /pmc/articles/PMC2695782/ /pubmed/19547700 http://dx.doi.org/10.1371/journal.pone.0006005 Text en Nakamuta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nakamuta, Juliana S.
Danoviz, Maria E.
Marques, Fabio L. N.
dos Santos, Leonardo
Becker, Claudia
Gonçalves, Giovana A.
Vassallo, Paula F.
Schettert, Isolmar T.
Tucci, Paulo J. F.
Krieger, Jose E.
Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title_full Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title_fullStr Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title_full_unstemmed Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title_short Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold
title_sort cell therapy attenuates cardiac dysfunction post myocardial infarction: effect of timing, routes of injection and a fibrin scaffold
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695782/
https://www.ncbi.nlm.nih.gov/pubmed/19547700
http://dx.doi.org/10.1371/journal.pone.0006005
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