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Adv Pharm Bull. 2021;11(4): 739-745.
doi: 10.34172/apb.2021.083
PMID: 34888221
PMCID: PMC8642797
Scopus ID: 85117269925
  Abstract View: 1210
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Research Article

Assessment of the Effect of Infliximab on Immunomodulation Properties of Mesenchymal Stem Cells In Vitro

Yasaman Aliasghari Sakha 1 ORCID logo, Ehsan Ehsani 2* ORCID logo, Elham Roshandel 3, Arsalan Jalili 3,4, Negar Vahdani 3, Abbas Hajifathali 3* ORCID logo

1 Developmental Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 Department of Biology, Roudhen Branch, Islamic Azad University, Tehran, Iran.
3 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
*Corresponding Authors: *Corresponding Author: Ehsan Ehsani; Email: , Email: e.ehsani@riau.ac.ir; *Corresponding Author: Abbas Hajifathali ; Email: , Email: a.hajifathali@sbmu.ac.ir

Abstract

Purpose: Mesenchymal stem cells (MSCs) have immunomodulatory traits making them a promising choice in the treatment of inflammatory diseases such as graft-versus-host disease (GVHD). Tumor necrosis factor-alpha (TNFα) is a major player of inflammatory disease which is blocked by infliximab to reduce the inflammation. The present study aims to assess the infliximab effects on the anti-inflammatory properties of MSCs.

Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs) were co-cultured with peripheral blood mononuclear cells (PBMCs) of GVHD patients in the presence of 10, 20 and 30 µg/mL of infliximab for 48 and 72 hours. The mRNA expression of indoleamine-2,3- dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), as well as the secreted amount of prostaglandin E2 (PGE2) in the culture supernatant, were examined.

Results: The results of this study show that the expression of IDO and iNOS genes, as well as the secretion amount of PGE2 in co-cultured groups raised dramatically, compared to the culture of BMMSCs or PBMCs alone. In co-culture groups containing infliximab, the expression of IDO and iNOS and also the amount of released PGE2 was significantly decreased compared to the control group without infliximab. However, no difference was found in the expression of assayed factors between 48 and 72 hours of treatments.

Conclusion: As an anti-TNFα agent, infliximab can decrease the inflammation in the microenvironment of MSCs, which might mitigate the immunomodulatory effects of MSCs. These effects of anti-inflammatory agents on the immunomodulatory capacity of MSCs should be considered in MSC therapy.




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Submitted: 10 Feb 2020
Revision: 10 May 2020
Accepted: 05 Aug 2020
ePublished: 05 Aug 2020
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