Pluripotent non-tumorigenic adipose tissue-derived Muse cells have immunomodulatory capacity mediated by TGFβ1

BARCALA TABARROZZI, AE; CORRALES, L; LABRIOLA, L; FUERTES, F; CUCCHIANI, R; SOGAYAR, MC; PERONE, MJ; GIMENO, L; ATTORRESI, AI; OLIVEIRA, TC; DEWEY, RA

Stem Cells Translational Medicine

AlphaMed Press

Año: 2016

Adult mesenchymal stromal cells (MSC)-based interventions have shown promising results in a broadrange of diseases. However, their use has faced limited effectiveness due to low survival rates andsusceptibility to environmental stress upon transplantation. Here, we describe cellular and molecularcharacteristics of Multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue(AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates. Muse-AT cellswere efficiently obtained by a simple, fast and affordable procedure, avoiding cell sorting and geneticmanipulation methods. Muse-AT cells isolated under severe cellular stress, expressed pluripotencystem cell markers and spontaneously differentiated into the three germ lineages. Muse-AT cells grownas spheroids have a limited proliferation rate, a diameter of ∼15μm and ultrastructural organizationsimilar to ES cells. Muse-AT cells evidenced a high SSEA-3 expression (∼60% of cells) after 7-10days 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 lowlevels of HLA-class II, CD45 and CD34. Using LPS-stimulated macrophages and antigen-challengedT cell assays, we have shown that Muse-AT cells have anti-inflammatory activities down-regulatingthe secretion of pro-inflammatory cytokines, such as IFNγ and TNFα. Muse-AT cells spontaneouslygained TGFβ1 expression that, in a pSMAD2-dependent manner, might prove pivotal in theirobserved 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 canpotentially be harnessed as immunoregulators to treat immune related disorders.