PMID- 28170177 OWN - NLM STAT- MEDLINE DCOM- 20190705 LR - 20190705 IS - 2157-6564 (Print) IS - 2157-6580 (Electronic) IS - 2157-6564 (Linking) VI - 6 IP - 1 DP - 2017 Jan TI - Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-beta1. PG - 161-173 LID - 10.5966/sctm.2016-0014 [doi] AB - 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 approximately 15 microm, and ultrastructural organization similar to that of embryonic stem cells. Muse-AT cells evidenced high stage-specific embryonic antigen-3 (SSEA-3) expression ( approximately 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-gamma and tumor necrosis factor-alpha. Muse-AT cells spontaneously gained transforming growth factor-beta1 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. CI - (c) 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. FAU - Gimeno, Maria L AU - Gimeno ML AD - Instituto de Investigacion en Biomedicina de Buenos Aires, National Scientific and Technical Research Council (CONICET), Partner Institute of the Max Planck Society, Buenos Aires, Argentina. FAU - Fuertes, Florencia AU - Fuertes F AD - Instituto de Investigacion en Biomedicina de Buenos Aires, National Scientific and Technical Research Council (CONICET), Partner Institute of the Max Planck Society, Buenos Aires, Argentina. FAU - Barcala Tabarrozzi, Andres E AU - Barcala Tabarrozzi AE AD - Instituto de Investigacion en Biomedicina de Buenos Aires, National Scientific and Technical Research Council (CONICET), Partner Institute of the Max Planck Society, Buenos Aires, Argentina. FAU - Attorressi, Alejandra I AU - Attorressi AI AD - Instituto de Investigacion en Biomedicina de Buenos Aires, National Scientific and Technical Research Council (CONICET), Partner Institute of the Max Planck Society, Buenos Aires, Argentina. FAU - Cucchiani, Rodolfo AU - Cucchiani R AD - Servicio de Cirugia Plastica, Hospital Austral, Derqui, Argentina. FAU - Corrales, Luis AU - Corrales L AD - Servicio de Cirugia Plastica, Hospital Austral, Derqui, Argentina. FAU - Oliveira, Talita C AU - Oliveira TC AD - Biochemistry Department, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brasil. FAU - Sogayar, Mari C AU - Sogayar MC AD - Cell and Molecular Therapy Center (Nucleo de Terapia Celular e Molecular/NETCEM), School of Medicine, University of Sao Paulo, Sao Paulo, Brasil. FAU - Labriola, Leticia AU - Labriola L AD - Biochemistry Department, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brasil. FAU - Dewey, Ricardo A AU - Dewey RA AD - Laboratorio de Terapia Genica y Celulas Madre, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico de Chascomus (IIB-INTECH), National Scientific and Technical Research Council, National University of General San Martin, Chascomus, Argentina. FAU - Perone, Marcelo J AU - Perone MJ AD - Instituto de Investigacion en Biomedicina de Buenos Aires, National Scientific and Technical Research Council (CONICET), Partner Institute of the Max Planck Society, Buenos Aires, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160802 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Smad2 Protein) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Adipose Tissue/*pathology MH - Animals MH - Biomarkers/metabolism MH - Carcinogenesis/drug effects/*pathology MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cytokines/metabolism MH - Germ Layers/cytology MH - Humans MH - *Immunomodulation/drug effects MH - Karyotype MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Phosphorylation/drug effects MH - Pluripotent Stem Cells/*cytology/transplantation MH - RAW 264.7 Cells MH - Signal Transduction/drug effects MH - Smad2 Protein/metabolism MH - Spleen/cytology MH - Stress, Physiological MH - Teratoma/pathology MH - Transforming Growth Factor beta1/*pharmacology PMC - PMC5442729 OTO - NOTNLM OT - Antigen-specific response OT - Immunomodulation OT - Spheroids/clusters OT - Stem cells OT - T lymphocytes EDAT- 2017/02/09 06:00 MHDA- 2019/07/06 06:00 PMCR- 2017/01/01 CRDT- 2017/02/08 06:00 PHST- 2016/01/10 00:00 [received] PHST- 2016/06/07 00:00 [accepted] PHST- 2017/02/08 06:00 [entrez] PHST- 2017/02/09 06:00 [pubmed] PHST- 2019/07/06 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - SCT312038 [pii] AID - 10.5966/sctm.2016-0014 [doi] PST - ppublish SO - Stem Cells Transl Med. 2017 Jan;6(1):161-173. doi: 10.5966/sctm.2016-0014. Epub 2016 Aug 2.