Academic Journal
Graft-Versus-Host Disease Amelioration by Human Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Is Associated with Peripheral Preservation of Naive T Cell Populations
| العنوان: | Graft-Versus-Host Disease Amelioration by Human Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Is Associated with Peripheral Preservation of Naive T Cell Populations |
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| المؤلفون: | Fujii, Sumie, Miura, Yasuo, Fujishiro, Aya, Shindo, Takero, Shimazu, Yutaka, Hirai, Hideyo, Tahara, Hidetoshi, Takaori-Kondo, Akifumi, Ichinohe, Tatsuo, Maekawa, Taira |
| المساهمون: | Ministry of Education, Culture, Sports, Science and Technology, Japan Agency for Medical Research and Development |
| المصدر: | Stem Cells ; volume 36, issue 3, page 434-445 ; ISSN 1066-5099 1549-4918 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2017 |
| الوصف: | A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs. In EV-treated GVHD mice, CD4+ and CD8+ T cells were suppressed. Importantly, the ratio of CD62L-CD44+ to CD62L + CD44- T cells was decreased, suggesting that BM-MSC-derived EVs suppressed the functional differentiation of T cells from a naive to an effector phenotype. BM-MSC-derived EVs also preserved CD4 + CD25 + Foxp3+ regulatory T cell populations. In a culture of CD3/CD28-stimulated human peripheral blood mononuclear cells with BM-MSC-derived EVs, CD3+ T cell activation was suppressed. However, these cells were not suppressed in cultures with EVs derived from normal human dermal fibroblasts (NHDFs). NHDF-derived EVs did not ameliorate the clinical or pathological characteristics of aGVHD in mice, suggesting an immunoregulatory function unique to BM-MSC-derived EVs. Microarray analysis of microRNAs in BM-MSC-derived EVs versus NHDF-derived EVs showed upregulation of miR-125a-3p and downregulation of cell proliferative processes, as identified by Gene Ontology enrichment analysis. Collectively, our findings provide the first evidence that amelioration of aGVHD by therapeutic infusion of BM-MSC-derived EVs is associated with the preservation of circulating naive T cells, possibly due to the unique microRNA profiles of BM-MSC-derived EVs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/stem.2759 |
| الاتاحة: | http://dx.doi.org/10.1002/stem.2759 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fstem.2759 https://onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2759 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/stem.2759 http://api.wiley.com/onlinelibrary/chorus/v1/articles/10.1002%2Fstem.2759 https://academic.oup.com/stmcls/article-pdf/36/3/434/42607158/stmcls_36_3_434.pdf |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.4C9BEA60 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/stem.2759 |
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