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Stem Cells International
Volume 2017, Article ID 9824698, 12 pages
https://doi.org/10.1155/2017/9824698
Research Article

In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets

1Stem Cell Laboratory, Fundamental Health Science Institute, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
2Post Graduate Program in Physiology, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
3Fundação Estadual de Produção e Pesquisa em Saúde, Porto Alegre, RS, Brazil
4Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
5Stem Cell Research Institute, Porto Alegre, RS, Brazil

Correspondence should be addressed to Patricia Pranke; rb.sgrfu@eknarpaicirtap

Received 26 October 2016; Revised 6 February 2017; Accepted 8 February 2017; Published 3 May 2017

Academic Editor: Benedetta Bussolati

Copyright © 2017 Régis Linhares Oliveira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of “off-the-shelf” clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated) allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets. The preactivation of MSCs upregulated the gene expression of anti-inflammatory molecules and also enhanced their immunomodulatory capacity in vitro. In vivo, allogeneic MSCs provoked an immunogenic response, with the infiltration of inflammatory cells at the transplant site and full graft rejection in both the untreated and preactivated groups. Allogeneic islets cotransplanted with preactivated MSCs prolonged graft survival for about 6 days, compared with islet alone. The present results corroborate the hypothesis that allogeneic MSCs are not immune-privileged and that after playing their therapeutic role they are rejected. Strategies that reduce allogeneic MSC immunogenicity can potentially prolong their in vivo persistence and improve the therapeutic effects.