title: What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
abstract: MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.
authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
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authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
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authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
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authors.affiliation: Helmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, Germany.
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authors.affiliation: Helmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, Germany.
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authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.
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authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.
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authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.
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authors.affiliation: Helmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation, Inhoffenstaße 7, 38124 Braunschweig, Germany.
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authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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authors.affiliation: ECBio S.A. - R&D in Biotechnology, Rua Henrique Paiva Couceiro, 27, 2700-451 Amadora, Portugal.
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