Regen Med Res
Volume 3, 2015
|Number of page(s)||12|
|Published online||30 September 2015|
Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model
Department of Immunology, Genetics and Pathology, Division of Clinical Immunology, Uppsala, Sweden
2 Department of Clinical Immunology and Transfusion Medicine, Karolinska Institutet and Hematology Center at Karolinska University Hospital, Huddinge, Sweden
3 Department of ,Immunology, Genetics and Pathology, The Rudbeck Laboratory, Dag Hammarskjölds Väg 20, SE-751 85 Uppsala, Sweden
* Correspondence: email@example.com
Received: 12 February 2015
Accepted: 18 September 2015
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 ILR2γnull mice and cellular interactions were investigated by confocal microscopy.
Result: 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.
Conclusion: 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.
Key words: Mesenchymal stromal cell / Islets of Langerhans / Transplantation / Endothelial cells
© 2015 Fransson et al.
Open Access This 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.
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