Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-β1

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Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-β1

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dc.contributor.author Gimeno, Maria.
dc.contributor.author Fuertes, Florencia.
dc.contributor.author Barcala, Andres.
dc.contributor.author Attorressi, Alejandra.
dc.contributor.author Cucchiani, Rodolfo.
dc.contributor.author Corrales, Luis.
dc.contributor.author Oliveira, Talita.
dc.date.accessioned 2020-02-18T19:01:46Z
dc.date.available 2020-02-18T19:01:46Z
dc.date.issued 2017-01-01
dc.identifier.citation Stem Cells Transl Med. 2017 Jan;6(1):161-173 en_US
dc.identifier.issn 2157-6564
dc.identifier.uri https://riu.austral.edu.ar/handle/123456789/814
dc.description.abstract Adult mesenchymal stromal cell-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness owing to the low survival rates and susceptibility to environmental stress on transplantation. We describe the cellular and molecular characteristics of multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue (AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates. Muse-AT cells were efficiently obtained using a simple, fast, and affordable procedure, avoiding cell sorting and genetic manipulation methods. Muse-AT cells isolated under severe cellular stress, expressed pluripotency stem cell markers and spontaneously differentiated into the three germ lineages. Muse-AT cells grown as spheroids have a limited proliferation rate, a diameter of ∼15 µm, and ultrastructural organization similar to that of embryonic stem cells. Muse-AT cells evidenced high stage-specific embryonic antigen-3 (SSEA-3) expression (∼60% of cells) after 7-10 days growing in suspension and did not form teratomas when injected into immunodeficient mice. SSEA-3+ -Muse-AT cells expressed CD105, CD29, CD73, human leukocyte antigen (HLA) class I, CD44, and CD90 and low levels of HLA class II, CD45, and CD34. Using lipopolysaccharide-stimulated macrophages and antigen-challenged T-cell assays, we have shown that Muse-AT cells have anti-inflammatory activities downregulating the secretion of proinflammatory cytokines, such as interferon-γ and tumor necrosis factor-α. Muse-AT cells spontaneously gained transforming growth factor-β1 expression that, in a phosphorylated SMAD2-dependent manner, might prove pivotal in their observed immunoregulatory activity through decreased expression of T-box transcription factor in T cells. Collectively, the present study has demonstrated the feasibility and efficiency of obtaining Muse-AT cells that can potentially be harnessed as immunoregulators to treat immune-related disorders. Stem Cells Translational Medicine 2017;6:161-173. en_US
dc.language.iso en en_US
dc.publisher Wiley Open Access en_US
dc.subject Antigen-specific response en_US
dc.subject Immunomodulation en_US
dc.subject Spheroids/clusters en_US
dc.subject Stem cells en_US
dc.title Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-β1 en_US
dc.type Article en_US


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