The Effects of Mesenchymal Stem Cells on the Gene Expression of TGF-beta and IFN-gamma in Patients with Rheumatoid Arthritis

Maryam  Rahimi-Khorashad; Mohsen Ghoryani; Arezoo Gowhari Shabgah; Zhaleh Shariati-Sarabi; Jalil Tavakkol-Afshari; Mojgan Mohammadi

doi:10.18502/ijaai.v22i2.12679

Maryam Rahimi-Khorashad Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Mohsen Ghoryani Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
Arezoo Gowhari Shabgah School of Medicine, Bam University of Medical Sciences, Bam, Iran
Zhaleh Shariati-Sarabi Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Jalil Tavakkol-Afshari Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Mojgan Mohammadi Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

DOI: https://doi.org/10.18502/ijaai.v22i2.12679

Keywords: Cytokines; Immunomodulation; Inflammation; Mesenchymal stem cells; Rheumatoid arthritis

Abstract

The therapeutic and immunomodulatory potential of mesenchymal stem cells (MSCs) in rheumatoid arthritis (RA) has attracted considerable scientific attention in recent decades. This study aimed to evaluate the expression of genes encoding interleukin (IL)4 and IL10, as well as interferon-gamma (IFNG) and transforming growth factor beta (TGFB1) in refractory RA patients following intravenous injection of autologous bone marrow-derived MSCs (BM-MSCs).

This study was registered in Iranian Registry of Clinical Trials (IRCT) (2015102824760N1) and ClinicalTrials.gov (identifier: NCT03333681). Blood samples were taken from 13 patients before and 1 and 6 months after the MSC injection to evaluate the clinical manifestations, paraclinical factors, and expression of IL4, IL10, IFNG, and TGFB1 genes employing the SYBR Green real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique.

There was a significant increase in the expression of TGFB1 at 1 and 6 months after the MSC injection compared to that in the baseline, while the expression of IL4 and IL10 did not change significantly. On the other hand, the expression of IFNG increased significantly after 1 month but decreased significantly at 6 months compared to 1 month after the intervention. Nevertheless, it showed no significant decrease compared to the baseline.

A significant decrease was observed for the expression of IFNG 6 months after the injection compared to that after 1 month, which was in concordance with the rise in the expression of the TGFB1 gene. A significant change in the gene expression of TGFB1 and IFNG in our study was consistent with the amelioration of clinical manifestations, suggesting a mechanism of action for MSCs in the treatment of RA.