Pluripotent non-tumorigenic adipose tissue-derived Muse cells have immunomodulatory capacity mediated by TGF-ß1

M.L. GIMENO; F. FUERTES; A.E. BARCALA TABARROZZI; A.I. ATTORRESSI; R. CUCCHIANI; L.CORRALES; T.C. OLIVEIRA; M.C. SOGAYAR; L. LABRIOLA; RICARDO A. DEWEY; MARCELO J. PERONE

Stem Cells Translational Medicine

AlphaMed Press

Año: 2017 vol. 6 p. 161 - 173

Adult mesenchymal stromalcells (MSC)-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness due to low survival rates and susceptibility to environmental stress upon transplantation. Here, we describe 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 by 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 ~15µm and ultrastructural organization similar to ES cells. Muse-AT cells evidenced a high SSEA-3 expression (~60% of cells) after 7-10 days growing in suspension and did not form teratomas when injected into immune-deficient mice. SSEA-3+-Muse-AT cells expressed CD105, CD29, CD73, HLA-class I, CD44 and CD90 and low levels of HLA-class II, CD45 and CD34. Using LPS-stimulated macrophages and antigen-challenged T cell assays, we have shown that Muse-AT cells have anti-inflammatory activities down-regulating the secretion of pro-inflammatory cytokines, such as IFNg and TNFa. Muse-AT cells spontaneously gained TGFb1 expression that, in a pSMAD2-dependent manner, might prove pivotal in their observed immunoregulatory activity through decreased expression of T-bet in T-cells. Collectively, the present study demonstrated the feasibility and efficiency of obtaining Muse-AT cells that can potentially be harnessed as immunoregulators to treat immune related disorders.