Mesenchymal stem cell secretome attenuates disease-associated microglial activation and cognitive decline in TBI-associated neuroinflammation.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Therapeutic options for traumatic brain injury (TBI) remain limited, in part due to injury-induced activation of microglia toward disease-associated microglia (DAM) phenotypes that contribute to persistent neuroinflammation and cognitive decline. We evaluated whether non-invasive intranasal delivery of mesenchymal stem cell secretome can enhance recovery after TBI by modulating microglial DAM signaling. Adult C57BL/6 mice underwent moderate controlled cortical impact (CCI) TBI. Adipose Stem Cell-derived Concentrated Conditioned Media (ASC-CCM) (∼20 ng protein/day, four doses) was administered intranasally, while sham and TBI controls received saline. Cognitive and memory functions assessed at 7 and 30 days post-injury showed TBI mice with impairments in learning, working, and long-term memory, while ASC-CCM-treated TBI mice performed similar to sham. These functional deficits correlated with increased astrogliosis (GFAP) and apoptosis (TUNEL), both of which were attenuated by ASC-CCM. TBI induced a time-dependent increase in astrocyte-associated APOE in the ipsilateral peri-lesion area and TYROBP in activated microglia near the impact site; ASC-CCM treatment significantly reduced both markers. Transcriptomic analysis of peri-lesion tissue at days 7 and 30 confirmed robust upregulation of DAM-associated genes (APOE, TYROBP, TREM2) after TBI, which was mitigated by intranasal ASC

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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