Mesenchymal Stromal Cells Mitigate Prolonged Cardiopulmonary Bypass-Induced Neuroinflammation

Kei Kobayashi, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.
Takuya Maeda, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.
Nemanja Saric, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.
Kamil Sarkislali, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.
Akihisa Furuta, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.
Chase D. McCann, Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, 20010, United States.
Patrick J. Hanley, Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, 20010, United States.
David Zurakowski, Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, United States.
Nobuyuki Ishibashi, Children's National Heart Center and Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, United States.

Document Type

Journal Article

Publication Date

11-6-2025

Journal

Interdisciplinary cardiovascular and thoracic surgery

Volume

40

Issue

11

DOI

10.1093/icvts/ivaf267

Keywords

cardiopulmonary bypass; cytokines; inflammation; mesenchymal stem cells; microglia

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.

Department

Pediatrics

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