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Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model

BACKGROUND: Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of i...

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Autores principales: Fransson, Moa, Brännström, Johan, Duprez, Ida, Essand, Magnus, Le Blanc, Katarina, Korsgren, Olle, Magnusson, Peetra U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589952/
https://www.ncbi.nlm.nih.gov/pubmed/26430512
http://dx.doi.org/10.1186/s40340-015-0010-9
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author Fransson, Moa
Brännström, Johan
Duprez, Ida
Essand, Magnus
Le Blanc, Katarina
Korsgren, Olle
Magnusson, Peetra U.
author_facet Fransson, Moa
Brännström, Johan
Duprez, Ida
Essand, Magnus
Le Blanc, Katarina
Korsgren, Olle
Magnusson, Peetra U.
author_sort Fransson, Moa
collection PubMed
description BACKGROUND: Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of islet transplantation to the abdominal muscle. Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2γ(null) mice and cellular interactions were investigated by confocal microscopy. RESULTS: The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, we show a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-islets compared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human islet endothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric blood vessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltrating macrophages. CONCLUSIONS: Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transduced human MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In this model of transplantation the MSC contribute to reduced fibrosis and increased islet endothelial cell migration. Furthermore, the MSC interact with the recipient vasculature and infiltrating macrophages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40340-015-0010-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-45899522015-10-02 Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model Fransson, Moa Brännström, Johan Duprez, Ida Essand, Magnus Le Blanc, Katarina Korsgren, Olle Magnusson, Peetra U. Regen Med Res Research BACKGROUND: Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of islet transplantation to the abdominal muscle. Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2γ(null) mice and cellular interactions were investigated by confocal microscopy. RESULTS: The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, we show a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-islets compared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human islet endothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric blood vessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltrating macrophages. CONCLUSIONS: Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transduced human MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In this model of transplantation the MSC contribute to reduced fibrosis and increased islet endothelial cell migration. Furthermore, the MSC interact with the recipient vasculature and infiltrating macrophages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40340-015-0010-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-30 /pmc/articles/PMC4589952/ /pubmed/26430512 http://dx.doi.org/10.1186/s40340-015-0010-9 Text en © Fransson et al. 2015 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
Fransson, Moa
Brännström, Johan
Duprez, Ida
Essand, Magnus
Le Blanc, Katarina
Korsgren, Olle
Magnusson, Peetra U.
Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title_full Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title_fullStr Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title_full_unstemmed Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title_short Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
title_sort mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589952/
https://www.ncbi.nlm.nih.gov/pubmed/26430512
http://dx.doi.org/10.1186/s40340-015-0010-9
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