Case Report
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4379-4384
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4379
Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with Crohn’s disease
Andrea Taddio, Alberto Tommasini, Erica Valencic, Ettore Biagi, Giuliana Decorti, Sara De Iudicibus, Eva Cuzzoni, Giuseppe Gaipa, Raffaela Badolato, Alberto Prandini, Andrea Biondi, Alessandro Ventura
Andrea Taddio, Alessandro Ventura, Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” - Trieste and University of Trieste, 34100 Trieste, Italy
Alberto Tommasini, Erica Valencic, Sara De Iudicibus, Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” - Trieste, 34100 Trieste, Italy
Ettore Biagi, Giuseppe Gaipa, Andrea Biondi, “Matilde Tettamanti” Research Centre, Laboratory of Cell Therapy “Stefano Verri”, Paediatric Clinic, University of Milano-Bicocca, San Gerardo Hospital, 20900 Monza, Italy
Giuliana Decorti, Sara De Iudicibus, Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Eva Cuzzoni, Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
Raffaela Badolato, Alberto Prandini, Department of Clinical and Experimental Sciences, Institute of Molecular Medicine “Angelo Nocivelli”, University of Brescia, 26122 Brescia, Italy
Author contributions: All authors contributed equally to this work; Taddio A, Tommasini A, Badolato R, Ventura A and Biondi A contributed to study concept and design, and to interpretation of the data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, obtaining the funding, administrative, technical, or material support, and study supervision; Biagi E, Valencic E, Decorti G, De Iudicibus S, Gaipa G, Cuzzoni E and Prandini A contributed to study concept and design, acquisition of the data, analysis of the data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, administrative, technical, or material support, and contributions to new reagents; Taddio A and Tommasini A wrote the paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrea Taddio, MD, Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” - Trieste and University of Trieste, via dell’Istria 65/1, 34100 Trieste, Italy. andrea.taddio@burlo.trieste.it
Telephone: +39-40-3785312 Fax: +39-40-3785290
Received: August 6, 2014
Peer-review started: August 8, 2014
First decision: August 27, 2014
Revised: September 30, 2014
Accepted: November 19, 2014
Article in press: November 19, 2014
Published online: April 14, 2015
Abstract

Mesenchymal stem cells (MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro. It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders. We present the case of a patient suffering from childhood-onset, multidrug resistant and steroid-dependent Crohn’s disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient’s peripheral blood mononuclear cells. Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation. The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

Keywords: Autoimmune disease, Crohn’s disease, Interferon-γ pretreatment, Mesenchymal stem cells, Immune regulation

Core tip: This is the first report of a lack of clinical response using interferon-γ pre-treated mesenchymal stem cell infusion in a patient with intractable Crohn’s disease. Data on the clinical effects of mesenchymal stem cell treatment in autoimmune disorders are sparse and usually report a good clinical response; however, since very few reports have been published, we think negative results are also worthy of attention. The use of mesenchymal stem cells pre-treated with interferon-γ is also of interest, and the lack of clinical benefit of bone marrow-derived interferon-γ pre-treated mesenchymal stem cell infusion has also been described, despite the lymphocyte immune regulation effect.