Anti-Inflammatory Effects of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in the Cortex and Striatum in a Nonalcoholic Steatohepatitis Model.

Abstract

Introduction: Brain injury associated with Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as an important health concern, yet effective therapeutic strategies remain limited. Recently, Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) and their Exosomes (AD-MSCExosomes) have attracted attention as promising therapeutic approaches. This study investigated the protective effects of AD-MSCs and their exosomes on the cortex and striatum in a mouse model of Non-Alcoholic Steatohepatitis (NASH).

Methods: Male C57BL/6 mice were fed a High-Fat Diet (HFD) for eight weeks to induce NASH. During the 6th, 7th, and 8th weeks, mice received intravenous injections of either 1×10⁶ AD-MSCs or 100 μg of exosomes. The percentage of degenerating cells in the cortex and striatum was assessed, and the gene expression levels of TNF-α, IL-1β, IL-10, and BDNF were evaluated in both brain regions.

Results: NAFLD significantly increased the percentage of degenerating cells in the cortex and striatum. Treatment with AD-MSCs and their exosomes markedly reduced cellular degeneration in both regions. In addition, NAFLD induced overexpression of BDNF and IL-1β in the cortex, as well as BDNF and TNF-α in the striatum, while IL-10 expression in the striatum was decreased. Most therapeutic interventions effectively reversed these alterations.

Discussion: The findings indicate that AD-MSCs and their exosomes may exert neuroprotective effects against NAFLD-associated brain injury, potentially through modulation of inflammatory pathways and reduction of neuronal degeneration in the cortex and striatum.

Conclusion: AD-MSCs and their exosomes attenuated brain tissue degeneration and modulated inflammatory cytokine expression in the cortex and striatum, suggesting their potential as therapeutic candidates for NAFLD-related neurological complications.