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

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  • AD-MSCs and their exosomes markedly reduced neuronal degeneration in both cortex and striatum in a high-fat diet NASH mouse model.
  • Treatment normalised inflammatory gene expression: reduced IL-1β and TNF-α overexpression and restored striatal IL-10, while modulating BDNF levels.
  • Findings support AD-MSCs and exosomes as promising therapeutic candidates for NAFLD-related brain injury via anti-inflammatory neuroprotection.
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Curr Stem Cell Res Ther. 2026 Sep 17. doi: 10.2174/011574888X431196260908071718. Online ahead of print.

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.

PMID:42770358 | DOI:10.2174/011574888X431196260908071718

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