Mesenchymal Stromal Cells Mitigate Prolonged Cardiopulmonary Bypass-Induced Neuroinflammation

Area of Science:

• Cardiovascular Surgery
• Neuroinflammation
• Regenerative Medicine

Background:

• Cardiopulmonary bypass (CPB) can induce systemic inflammation and microglial activation.
• The efficacy of bone marrow-derived mesenchymal stromal cells (BM-MSCs) in mitigating extensive inflammatory reactions during CPB requires further investigation.

Purpose of the Study:

• To assess the effectiveness of BM-MSC treatment in managing extensive inflammatory responses associated with prolonged CPB.
• To investigate the impact of BM-MSCs on microglial activation and inflammatory markers in the brain following CPB.

Main Methods:

• Two-week-old piglets underwent CPB with or without deep hypothermic circulatory arrest (DHCA) and BM-MSC administration.
• BM-MSCs (1 × 10^7 cells/kg) were administered via the CPB circuit during rewarming.
• Plasma cytokines, microglial activation in brain tissue, and gene expression in the premotor cortex were analyzed.

Main Results:

• Extended CPB significantly increased white matter microglia and plasma levels of interferon-gamma (IFN-γ) and TNF-α.
• BM-MSC treatment normalized microglia expansion and modulated cytokine profiles, including reduced IFN-γ and increased IL-10, IL-1β, and IL-8.
• Correlations indicated a positive association between IFN-γ and microglial activation, and inverse correlations between IL-10, IL-1β, IL-8, and microglial activation.

Conclusions:

• BM-MSC administration via CPB effectively reduces extensive inflammatory stress and microglial activation.
• This model provides a platform for studying CPB-induced neuroinflammation and the therapeutic mechanisms of BM-MSCs.