Is human umbilical cord mesenchymal stem cell-derived conditioned medium effective against oxidative and inflammatory status in CCl4-induced acute liver injury?

ABSTRACT

INTRODUCTION: Acute liver injury (ALI) is diagnosed by detection of elevated liver enzymes within six months after liver damage. Mesenchymal stem cells (MSCs) have recently been considered a beneficial strategy for treating various diseases due to healing secretory factors. Therapeutic effects of human umbilical cord MSCs-derived conditioned medium (hMSC-CM) were evaluated on CCl4-induced ALI. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into groups including N (received saline), ALI (received CCl4), RPMI (received CCl4 and RPMI medium), and ALI-CM (received CCl4 and hMSC-CM) groups. The expression of TNF-α and TGFß-1 genes was evaluated with qPCR. Hepatic levels of TNF-α and TGF-ß were measured by ELISA. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), glutathione peroxidase (GPx) activity, and catalase (CAT) activity were also assayed. Hematoxylin-eosin (H&E), Masson's trichrome, reticulin, and Periodic Acid-Schiff (PAS) stainings were conducted to evaluate tissue lesions. RESULTS: CCl4 increased expression of TNF-α and TGF-1ß at both mRNA and protein levels, while hMSC-CM decreased these parameters in the ALI-CM group. TAC levels significantly decreased in the ALI group, and CCl4 increased TOS and MDA levels compared with the N group. hMSC-CM treatment led to the return of these parameters to their baseline levels. GPx and CAT activity in the ALI group were significantly lower than in the N group and hMSC-CM reduced these parameters to the baseline in the ALI-CM group. hMSC-CM modulated CCl4-induced tissue lesions. CONCLUSION: The present study suggests hMSC-CM probably improves CCl4-induced ALI through its antioxidant and anti-inflammatory effects.