الفهرس 
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Abstract
The healing potential of MSCs has been demonstrated in numerous lung injury models, however, whether MSCs could be effective for alleviating PF induced by AD remains largely unknown. Additionally, the time period required for MSCs to accomplish maximal mitigative efficacy and the mechanisms by which MSCs engraftment ameliorates lung injury have not been clearly explored. Moreover, the effectiveness of CM derived form MSCs in the moderation of PF remains controversial and no prior study has investigated the restorative indications of MSCs-derived CM in a rat model of PF induced by AD.
We aimed to evaluate the potential curative influence of BM-MSCs, in comparison to CM, on PF induced by AD in rats.
To achieve this goal, BM-MSCs were isolated from adult male Wistar rats, cultured, passaged, characterized and labeled. Also, CM from cultured BM-MSCs were collected and concentrated.
The experimental design was constructed as follows: sixty-four adult male Wistar rats were randomly divided into eight groups: negative control group (saline), PF model group (AD), AD groups treated with BM-MSCs which were left for 1, 2 and 4 months as well as AD groups treated with CM which were left for 1, 2 and 4 months.
The biochemical investigations included serum macrophage inflammatory protein 2 (MIP-2), Clara cell secretory protein (CC16) and keratinocyte growth factor (KGF) levels, which were determined by commercial enzyme-linked immunosorbent assays.
The molecular analyses included gene expression levels of type I collagen (COL1A1), connective tissue growth factor (CTGF), transforming growth factor beta 1 (TGF-β1), mothers against decapentaplegic homolog 3 (SMAD3) and S100 calcium-binding protein A4 (S100A4), which were detected in lung tissues using quantitative real-time polymerase chain reaction.
The histopathological examinations included Hematoxylin & eosin, Masson’s trichrome and prussian blue staining of lung tissue sections to assess lung injury, collagen deposition and distribution of transplanted BM-MSCs, respectively.The outcomes of the present study indicated that:
1) There was a significant increase in serum levels of MIP2, CC16 and KGF in AD-administered rats when compared to their counterparts.
2) A significant increase in lung COL1A1, CTGF, TGF-β1, SMAD3 and S100A4 transcript levels, was noted in AD-administered rats when compared to the controls.
3) Treatment of AD-administered rats with BM-MSCs or CM resulted in a significant:
a) Increase in KGF levels accompanied by a significant decrease in MIP-2 and CC16 levels;
b) Decrease in the lung expression of COL1A1, CTGF, TGF-β1, SMAD3 and S100A4;
c) Histological amelioration in the extent of lung injury;
d) Decrease in the extent of lung collagen deposition.
4) Treatment with BM-MSCs exhibited a superior mitigative effect to CM against PF.
5) Among BM-MSCs and CM treatment groups, 2 and 4 months’ post-treatment periods demonstrated better fibrosis-attenuating influence than 1-month post-treatment period.