Conditioned Medium from Human Amniotic Membrane-Derived Mesenchymal Stem Cells Modulates Inflammatory and Myofibrotic Factors in Vivo.

Abstract

Background: Heart failure (HF) is a prevalent diagnosis with a significant mortality rate. Various therapeutic approaches exist for treating HF, and human adipose-derived mesenchymal stem cells-conditioned medium (hAMSCs-CM) therapy has emerged as a promising option. Despite its potential efficacy, the precise mechanism of action underlying hAMSCs-CM treatment remains unclear. To address this knowledge gap, we conducted a novel animal study to investigate the mechanism of action of hAMSCs-CM in an HF model, with a specific focus on transforming growth factor-β (TGF-β)/galectin-3, monocyte chemoattractant protein-1 (MCP1), B-type natriuretic peptide (BNP), and aldosterone (ALD).

Methods: Forty adult male Wistar rats were divided into 4 groups: control, HF, culture medium, and CM. All rats, except those in the control group, received an injection of isoproterenol to induce an animal model of HF. The CM group was administered the CM, while those in the culture medium group received standard culture media. Subsequently, serum levels of fibrotic factors, including TGF-β/galectin-3, MCP1, BNP, and ALD, were measured using ELISA. Statistical analysis was performed using one-way analysis of variance and the Tukey test.

Results: Serum levels of TGF-β/galectin-3, MCP1, BNP, and ALD were significantly elevated in the HF, CM, and culture medium groups compared with the control group (P<0.001). Additionally, these fibrotic factors were significantly reduced in the CM group compared with the HF group (P<0.001). Notably, CM therapy could not restore TGF-β/galectin-3, MCP1, BNP, or ALD levels to the normal range observed in the control group.

Conclusion: Our findings indicate that hAMSCs-CM modulates the expression of inflammatory and fibrotic cytokines, such as TGF-β/galectin-3, MCP1, BNP, and ALD, in isoproterenol-induced HF in male rats. These results contribute to a better understanding of the therapeutic mechanisms underlying hAMSCs-CM treatment for HF.