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Mesenchymal Stromal Cells Mitigate Prolonged Cardiopulmonary Bypass-Induced Neuroinflammation

Year: 2025

Type: article

Abstract: OBJECTIVES: Bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery through cardiopulmonary bypass (CPB) can modulate CPB-induced systemic inflammation and inhibit microglial activation. The present study assessed whether BM-MSC treatment remains effective for extensive inflammatory reactions. METHODS: Two-week-old piglets were randomized into control, CPB with deep hypothermic circulatory arrest (DHCA), CPB with BM-MSCs, CPB with DHCA plus 180 min extended perfusion, and extended CPB with BM-MSCs. Human BM-MSCs (1 × 107 cells/kg) were delivered via the CPB circuit during rewarming. We measured 9 porcine plasma cytokines. Brains were harvested for microglial immunohistochemistry and premotor cortex RNA-sequencing. RESULTS: A total of 20 piglets were included (n = 4 per group). An extended CPB period increased the number of white matter microglia and plasma interferon-g (IFN-g) and TNF-a levels compared to standard CPB (P < .05). Notably, BM-MSCs normalized the extensive microglia expansion resulting from prolonged CPB (P < .001). In addition to reduced IFN-g and increased IL-10, BM-MSCs increased IL-1b and IL-8 levels, suggesting possible immunosuppressive reactions observed under inflammatory microenvironment. Gene ontology analyses in the premotor cortex post-CPB found involvement of NF-kB signalling. While there was a positive correlation between IFN-g and microglia expansion/activation, IL-10 levels were inversely correlated with the number of microglia. Consistent with immunosuppressive roles in the inflammatory environment, we found inverse correlations between IL-1b and IL-8 levels and CPB-induced microglial activation (P < .01). CONCLUSIONS: BM-MSC administration via CPB shows promise for reducing extensive inflammatory stress. Further investigation using this model will elucidate CPB-induced unique pathological events in the developing brain and mechanisms underlying the therapeutic actions of BM-MSC.

Source: Interdisciplinary CardioVascular and Thoracic Surgery

DOI: 10.1093/icvts/ivaf267