International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro

  • Daiana V. Lopes Alves (Institute of Biomedical Sciences, Federal University of Rio de Janeiro) ;
  • Cesar Claudio-da-Silva (Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro) ;
  • Marcelo C. A. Souza (Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro) ;
  • Rosa T. Pinho (Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ) ;
  • Wellington Seguins da Silva (Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ) ;
  • Periela S. Sousa-Vasconcelos (Laboratory of Clinical Immunology, Oswaldo Cruz Institute, FIOCRUZ) ;
  • Radovan Borojevic (Institute of Biomedical Sciences, Federal University of Rio de Janeiro) ;
  • Carmen M. Nogueira (Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro) ;
  • Helio dos S. Dutra (Institute of Biomedical Sciences, Federal University of Rio de Janeiro) ;
  • Christina M. Takiya (Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro) ;
  • Danielle C. Bonfim (Institute of Biomedical Sciences, Federal University of Rio de Janeiro) ;
  • Maria Isabel D. Rossi (Institute of Biomedical Sciences, Federal University of Rio de Janeiro)
  • Received : 2022.10.12
  • Accepted : 2023.04.04
  • Published : 2023.11.30
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Abstract

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.

Keywords

Acknowledgement

We thank Dr. Wagner Baetas da Cruz for providing the scientific protocol for CD206 immmunohistochemistry; Dr. Vivian Samoto for technical assistance during immunohistochemistry experiments; Dr. Alex Duarte for providing the protocol for intracellular cytokine analysis; and the Multiuser FACS Facility of the Health Sciences Center of the Federal University of Rio de Janeiro for assistance during cell sorting experiments. This work was supported by grants from the Brazilian government agencies FAPERJ, CAPES, and CNPq. The sponsors had no role in study design, data collection and analysis, decision to publish or manuscript preparation.

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