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Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2011 (English)In: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 13, no 3, 269-278 p.Article in journal (Refereed) Published
Abstract [en]

Background aims. Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties. Methods. We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)gamma gamma. Results. Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-gamma gamma increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC. Conclusions. Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.

Place, publisher, year, edition, pages
2011. Vol. 13, no 3, 269-278 p.
Keyword [en]
Apoptosis, cytotoxicity, immunomodulation, immunosuppression, in utero transplantation, mesenchymal stromal cells, natural killer cell-mediated lysis, pre-natal transplantation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149040DOI: 10.3109/14653249.2010.523077ISI: 000287313200003PubMedID: 20942778OAI: oai:DiVA.org:uu-149040DiVA: diva2:403863
Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11Bibliographically approved

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