Cargando…
The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate
BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407025/ https://www.ncbi.nlm.nih.gov/pubmed/28446216 http://dx.doi.org/10.1186/s13287-017-0545-y |
_version_ | 1783232079171944448 |
---|---|
author | Grudzenski, Saskia Baier, Sebastian Ebert, Anne Pullens, Pim Lemke, Andreas Bieback, Karen Dijkhuizen, Rick M. Schad, Lothar R. Alonso, Angelika Hennerici, Michael G. Fatar, Marc |
author_facet | Grudzenski, Saskia Baier, Sebastian Ebert, Anne Pullens, Pim Lemke, Andreas Bieback, Karen Dijkhuizen, Rick M. Schad, Lothar R. Alonso, Angelika Hennerici, Michael G. Fatar, Marc |
author_sort | Grudzenski, Saskia |
collection | PubMed |
description | BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 10(6) cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI). METHODS: Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 10(6), 3 × 10(5), or 5 × 10(4) ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis. RESULTS: The ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of stroke volumes revealed an increased infarction after injection of 1 × 10(6) ASCs compared to controls or application of 5 × 10(4) ASCs (p < 0.05). At 9 days post-MCAo, injection of 3 × 10(5) ASCs resulted in reduced infarct volumes (p < 0.05). Correspondingly, MRI analysis revealed no changes in cell numbers between both MRI examinations but showed active ASC migration to the site of infarction. CONCLUSION: Our results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 10(6) cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0545-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5407025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54070252017-05-02 The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate Grudzenski, Saskia Baier, Sebastian Ebert, Anne Pullens, Pim Lemke, Andreas Bieback, Karen Dijkhuizen, Rick M. Schad, Lothar R. Alonso, Angelika Hennerici, Michael G. Fatar, Marc Stem Cell Res Ther Research BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 10(6) cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI). METHODS: Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 10(6), 3 × 10(5), or 5 × 10(4) ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis. RESULTS: The ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of stroke volumes revealed an increased infarction after injection of 1 × 10(6) ASCs compared to controls or application of 5 × 10(4) ASCs (p < 0.05). At 9 days post-MCAo, injection of 3 × 10(5) ASCs resulted in reduced infarct volumes (p < 0.05). Correspondingly, MRI analysis revealed no changes in cell numbers between both MRI examinations but showed active ASC migration to the site of infarction. CONCLUSION: Our results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 10(6) cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0545-y) contains supplementary material, which is available to authorized users. BioMed Central 2017-04-26 /pmc/articles/PMC5407025/ /pubmed/28446216 http://dx.doi.org/10.1186/s13287-017-0545-y Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Grudzenski, Saskia Baier, Sebastian Ebert, Anne Pullens, Pim Lemke, Andreas Bieback, Karen Dijkhuizen, Rick M. Schad, Lothar R. Alonso, Angelika Hennerici, Michael G. Fatar, Marc The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title | The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title_full | The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title_fullStr | The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title_full_unstemmed | The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title_short | The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
title_sort | effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407025/ https://www.ncbi.nlm.nih.gov/pubmed/28446216 http://dx.doi.org/10.1186/s13287-017-0545-y |
work_keys_str_mv | AT grudzenskisaskia theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT baiersebastian theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT ebertanne theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT pullenspim theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT lemkeandreas theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT biebackkaren theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT dijkhuizenrickm theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT schadlotharr theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT alonsoangelika theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT hennericimichaelg theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT fatarmarc theeffectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT grudzenskisaskia effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT baiersebastian effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT ebertanne effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT pullenspim effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT lemkeandreas effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT biebackkaren effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT dijkhuizenrickm effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT schadlotharr effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT alonsoangelika effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT hennericimichaelg effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate AT fatarmarc effectofadiposetissuederivedstemcellsinamiddlecerebralarteryocclusionstrokemodeldependsontheirengraftmentrate |