Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumat
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ORIGINAL ARTICLE
Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumatoid arthritis Heba El-Gendy 1 & Salah El-Deen Hawass 1 & Manal Awad 1 & Mona Ahmad Mohsen 1 & Maha Amin 2 & Hussein Abdelaziz Abdalla 3 & Samah Fouad 4 & Ahmed Lotfy 5
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract To compare human adipose tissue mesenchymal stem cells (AT-MSCs) and etanercept as immunomodulatory agents for collagen-induced arthritis (CIA). CIA was induced by rats’ immunization with collagen type II (CII) in complete Freund’s adjuvant in days 0 and 7. Before the onset of CIA, prevention group received five doses of AT-MSCS intraperitoneally. After establishment of arthritis, rats received either five doses of AT-MSCs or phosphate-buffered saline (PBS) intraperitoneally or six doses of etanercept subcutaneously. Clinical and histopathological evaluation were performed in all groups; serum levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and anti-collagen II were assessed by enzyme-linked immunosorbent assay (ELISA). A total percent of autoreactive T and regulatory T (Treg) cells were quantified using spleen immune histochemical analysis. AT-MSCs were able to delay the onset of CIA, suppress the ongoing clinical and histopathological signs, decrease serum levels of TNF-α and anti-collagen type II, and downregulate the autoreactive T cells as etanercept. AT-MSCs were more potent in Treg cells upregulation, producing high serum levels of IL10. AT-MSCs might have a therapeutic effect in CIA via their potency in immune cell education, representing an effective new promising approach in rheumatoid arthritis in human. Keywords Mesenchymal stem cells . CIA . Rheumatoid arthritis . Etanercept . Regulatory T cells
Highlights • AT-MSCs could delay and suppress both clinical and histopathological features of rat CIA. • AT-MSCs were proven to be an immunomodulatory agent that reestablish immunologic tolerance in CIA. • AT-MSCs may require sufficient time for migration to lymphoid organs to target the immune cells. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12026-020-09132-w) contains supplementary material, which is available to authorized users. * Heba El-Gendy [email protected] Salah El-Deen Hawass [email protected] Manal Awad [email protected] Mona Ahmad Mohsen [email protected]
Maha Amin [email protected] Hussein Abdelaziz Abdalla [email protected] Samah Fouad [email protected] Ahmed Lotfy [email protected] Extended author information available on the last page of the article
Immunol Res
Introduction
Animals of the study
Rheumatoid arthritis (RA) is a systemic autoimmune disorder, characterized by chronic inflammation of synovial joints, as well as cartilage and bone damage. The breakdown of the immunologic self-tolerance results in aberrant immune responses directed at self-antigens in the joints [1]. Current treatment strate
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