| Autor: |
Lopes Alves DV; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Integrated Laboratory of Morphology, Institute of Biodiversity and Sustainability, NUPEM, Federal University of Rio de Janeiro, Macaé, RJ, Brazil., Claudio-da-Silva C; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Surgery Department, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Souza MCA; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Surgery Department, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Pinho RT; Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil., da Silva WS; Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil., Sousa-Vasconcelos PS; Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil., Borojevic R; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Nogueira CM; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Dutra HDS; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Takiya CM; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Bonfim DC; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Rossi MID; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.; Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. |
| Abstrakt: |
Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68 ＋ /FXIII-A - inflammatory pool. Despite it, in vitro , coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF- α ＋ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations. |
