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

OBJECTIVE

Pulmonary toxicity induced by CCl, 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 l), olive oil (1 ml/kg), and hMSC-CM (100 g protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl (1 ml/kg) and 100 g protein/kg IV hMSC-CM. While the treatment with olive oil and CCl 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 4 to week 12. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-), and transforming growth factor-1 (TGF-1) genes, and proteins expression by real-time RCR and western blotting, respectively.

RESULTS

Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-), transforming growth factor-b1 (TGF-1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups ( ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups ( ≤ 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 CCl-induced pulmonary fibrosis.