Tayebeh Mahmoudi
1,2 
, Kamal Abdolmohammadi
1,2,3* , Hamed Bashiri
2,4 , Mehdi Mohammadi
2,5, Mohammad Jafar Rezaie
1 , Fardin Fathi
1 , Shohreh Fakhari
1,2 , Mohammad Ali Rezaee
6,4, Ali Jalili
7,2* , Mohammad Reza Rahmani
6,2*, Lobat Tayebi
81 Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
2 Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
3 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
4 Department of Medical Laboratory Sciences, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran.
5 Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
6 Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
7 Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
8 Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.
*Corresponding Author: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Email k_abdolmohammadi@razi.tums.ac.ir, Ali130@gmail.com, rahmany191@gmail.com
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 H2 O2 -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 H2 O2 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