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Author Spotlight: Simulating Pediatric Cardiac Surgery Using a Neonatal Piglet Model
Published on: May 26, 2023
Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model
Kamil Sarkislali1,2, Kei Kobayashi1,2,3, Nemanja Sarić1,2
1Center for Neuroscience Research, Children's National Hospital, Washington, DC, USA.
Insights
Mesenchymal stromal cells (MSCs) administered during heart surgery reduce brain inflammation and improve neurodevelopment in infants with congenital heart disease (CHD). This therapy minimizes microglial activation and neuronal damage, offering a promising treatment for neurological impairments.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pediatric Cardiology
Background:
- Cardiopulmonary bypass (CPB) in neonates with congenital heart disease (CHD) induces oxidative and inflammatory stresses.
- These stresses lead to sustained microglia activation and cortical dysmaturation, contributing to neurodevelopmental deficits.
- Current treatments lack targeted neuroprotective strategies for infants undergoing cardiac surgery.
Purpose of the Study:
- To investigate the neuroprotective effects of mesenchymal stromal cells (MSCs) delivered during CPB in a neonatal model of cardiac surgery.
- To elucidate the mechanisms underlying MSC-mediated neuroprotection, focusing on microglial activation and neuronal apoptosis.
- To assess the impact of MSC treatment on cortical maturation and behavioral outcomes post-surgery.
Main Methods:
- Neonatal rats underwent surgical procedures mimicking cardiac surgery with CPB.
- Mesenchymal stromal cells (MSCs) were administered via CPB.
- Microglial activation, neuronal apoptosis, cortical development, and behavioral assessments were evaluated.
- Transcriptomic analysis was performed to identify molecular mediators.
Main Results:
- MSC delivery significantly reduced microglial activation and neuronal apoptosis in the developing cortex.
- MSC treatment improved cortical dysmaturation and normalized behavioral alterations observed after surgery.
- Exosome-derived microRNAs (miRNAs) were implicated as key mediators, potentially through STAT3 signaling pathways.
- MSC therapy demonstrated significant neuroprotective effects, mitigating CPB-induced brain injury.
Conclusions:
- Mesenchymal stromal cell (MSC) therapy administered during cardiopulmonary bypass offers significant neuroprotection in neonatal cardiac surgery.
- MSC treatment ameliorates microglial activation, neuronal apoptosis, and cortical dysmaturation, leading to improved neurological outcomes.
- Exosome-mediated transfer of miRNAs represents a critical mechanism for MSCs' therapeutic effects in this context.
- MSC therapy holds translational potential for improving neurodevelopmental outcomes in children with congenital heart disease.
Abstract:
Oxidative/inflammatory stresses due to cardiopulmonary bypass (CPB) cause prolonged microglia activation and cortical dysmaturation, thereby contributing to neurodevelopmental impairments in children with congenital heart disease (CHD). This study found that delivery of mesenchymal stromal cells (MSCs) via CPB minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Furthermore, transcriptomic analyses suggest that exosome-derived miRNAs may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation. Our findings demonstrate that MSC treatment during cardiac surgery has significant translational potential for improving cortical dysmaturation and neurological impairment in children with CHD.
