Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

Author(s)

Larocca, Rafael Assumpcao ^{[1, 2]} ; Moraes-Vieira, Pedro Manoel ^{[1, 3]} ; Bassi, Enio Jose ^[1] ; Semedo, Patricia ^[4] ; de Almeida, Danilo Candido ^[4] ; da Silva, Marina Burgos ^[1] ; Thornley, Thomas ^[2] ; Pacheco-Silva, Alvaro ^{[4, 5]} ; Saraiva Camara, Niels Olsen ^{[4, 1]}

Affiliation

^[1] Univ Sao Paulo, Lab Transplantat Immunobiol, Dept Immunol, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Transplant Inst, Boston, MA 02215 - USA

^[3] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Div Endocrinol, Boston, MA 02215 - USA

^[4] Univ Fed Sao Paulo, Lab Clin & Expt Immunol, Div Nephrol, Sao Paulo - Brazil

^[5] Albert Einstein Hosp, Inst Israelita Ensino & Pesquisa, Renal Transplantat Div, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 10 OCT 4 2013.
• Web of Science Citations: 24

Abstract

Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4(+) regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naive CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation. (AU)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 06/55326-4 - TCD4+regulatory cell induction by mesenchymal stem cells
• Grantee: Rafael Assumpção Larocca
• Support Opportunities: Scholarships in Brazil - Doctorate