Author/Authors :
Mahmoudi, Tayebeh Cellular and Molecular Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj - Department of Immunology - Faculty of Medicine - Kurdistan University of Medical Sciences, Sanandaj , Abdolmohammadi, Kamal Department of Immunology - School of Medicine - Tehran University of Medical Sciences - Cellular and Molecular Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj - Department of Immunology - Faculty of Medicine - Kurdistan University of Medical Sciences, Sanandaj , Bashiri, Hamed Department of Medical Laboratory Sciences - Faculty of Paramedical - Kurdistan University of Medical Sciences, Sanandaj - Department of Immunology - Faculty of Medicine - Kurdistan University of Medical Sciences, Sanandaj , Mohammadi, Mehdi Department of Immunology - School of Public Health - Tehran University of Medical Sciences, Tehran , Rezaie, Mohammad Jafar Cellular and Molecular Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj , Fathi, Fardin Cellular and Molecular Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj , Fakhari, Shohreh Cellular and Molecular Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj - Department of Immunology - Faculty of Medicine - Kurdistan University of Medical Sciences, Sanandaj , Rezaee, Mohammad Ali Zoonoses Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj , Jalili, Ali Cancer and Immunology Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj , Rahmani, Mohammad Reza Zoonoses Research Center - Research Institute for Health Development - Kurdistan University of Medical Sciences, Sanandaj , Tayebi, Lobat Marquette University School of Dentistry - Milwaukee - WI - 53233 - USA
Abstract :
Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available
treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic
potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve
their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic
effects of H2O2-preconditioned MSCs (p-MSCs) on mice with bleomycin-induced
pulmonary fibrosis (PF).
Methods: Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation
of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and
exposed to a sub-lethal concentration (15 μM for 24 h) of H2O2 in vitro. One week following the
injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The
survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were
sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO)
activity, histopathological changes (hematoxylin-eosin and Masson’s trichrome) and expression
of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through
immunohistochemistry (IHC) staining.
Results: Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased
connective tissue (P < 0.05) and collagen deposition. Additionally, it is determined that lung tissue
in the PF+pMSC group has increased alveolar space (P < 0.05) and diminished expression of
TGF-β1 and α-SMA.
Conclusion: The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic
factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in
IPF.
Keywords :
Pulmonary fibrosis (PF) , Bleomycin (BLM) , Mesenchymal stem cells (MSCs) , Myeloperoxidase (MPO) , Hydrogen peroxide (H2O2)
