The Restoring Effect of Human Umbilical Cord-Derived Mesenchymal Cell-Conditioned Medium (hMSC-CM) against Carbon Tetrachloride-Induced Pulmonary Fibrosis in Male Wistar Rats

• Published in: International journal of inflammation 2022-12, Vol.2022, p.7179766-10
• Main Authors: Khajvand-Abedini, Maryam, Bahmani, Mahdi, Ziamajidi, Nasrin, Nourian, Alireza, Habibi, Parisa, Heidarisasan, Shirin, Abbasalipourkabir, Roghayeh
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Carbon tetrachloride; Collagen; Cytokines; Ethylenediaminetetraacetic acid; Experiments; Growth factors; Medical research; Olive oil; Oxidases; Proteins; Pulmonary fibrosis; Reagents; Rodents; Sampling; Statistical analysis; Stem cells; Steroids; Transforming growth factors; Tumor necrosis factor-TNF; Umbilical cord
• ISSN: 2090-8040; 2042-0099; 2042-0099
• DOI: 10.1155/2022/7179766

Objective. Pulmonary toxicity induced by CCl4, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent. Methods. Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 µl), olive oil (1 ml/kg), and hMSC-CM (100 μg protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl4 (1 ml/kg) and 100 μg protein/kg IV hMSC-CM. While the treatment with olive oil and CCl4 was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4th to week 12th. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β1 (TGF-β1) genes, and proteins expression by real-time RCR and western blotting, respectively. Results. Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), transforming growth factor-b1 (TGF-β1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (p≤0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (p≤0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group. Conclusion. hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl4-induced pulmonary fibrosis.