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Mesenchymal stromal cells supportendothelial cell interactions in anintramuscular islet transplantation model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Mag)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Magnusson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Magnusson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Essand)ORCID iD: 0000-0002-9725-0422
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2015 (English)In: Regenerative Medicine Research, ISSN 2050-490X, Vol. 3, UNSP 1Article in journal (Refereed) Published
Abstract [en]

Background:

Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies andhave lately been in focus as immunosuppressive actors in the field of transplantation. Herein we haveextended our previously published in vitro model of MSC-islets in an experimental setting of islettransplantation to the abdominal muscle.Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscletissue of NOD-scid ILR2γnull mice and cellular interactions were investigated by confocal microscopy.

Results:

The MSC reduced fibrotic encapsulation and facilitated endothelial cell interactions. In particular, weshow a decreased fraction of αSMA expressing fibrotic tissue surrounding the graft in presence of MSC-isletscompared to islets solely distributed into the muscle tissue. Also, in the presence of MSC, human isletendothelial cells migrated from the center of the graft out into the surrounding tissue forming chimeric bloodvessels with recipient endothelial cells. Further, in the graft periphery, MSC were seen interacting with infiltratingmacrophages.

Conclusions:

Here, in our experimental in vivo model of composite human islets and luciferase-GFP-transducedhuman MSC, we enable the visualization of close interactions between the MSC and the surrounding tissue. In thismodel 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.

Place, publisher, year, edition, pages
2015. Vol. 3, UNSP 1
Keyword [en]
Mesenchymal stromal cell, endothelial cells, islets of Langerhans, transplantation
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-276979DOI: 10.1186/s40340-015-0010-9ISI: 000363658500001OAI: oai:DiVA.org:uu-276979DiVA: diva2:903786
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2017-01-25Bibliographically approved

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Fransson, MoaBrännström, JohanEssand, MagnusKorsgren, OlleMagnusson, Peetra

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