Mesenchymal Stromal Cells Improve Postoperative Cardiac Dysmaturation in a Juvenile Porcine Model

Mesenchymal stromal cells (MSCs) are known to protect tissues from inflammation and oxidative stress. This study aimed to evaluate the effects of cardiopulmonary bypass (CPB) and MSC treatment on cardiac maturation in a juvenile porcine model.

Two-week-old Yorkshire pigs were randomly assigned to 3 groups: (1) control (n=10), (2) CPB (n=10), and (3) CPB + MSC (n=15). MSCs (1 × 10⁷ cells/kg) were administered via CPB. Acute and long-term responses were evaluated at 3 hours and 4 weeks post-CPB. In addition to histological analysis, diffusion tensor imaging was used to assess cardiac microstructures.

Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and Iba1⁺ (ionized calcium-binding adapter molecule 1) monocytes/macrophages increased at 3 hours post-CPB compared with controls. The increases in cardiac 8-OHdG and monocytes/macrophages were still observed at 4 weeks, indicating prolonged oxidative/inflammatory stresses resulting from CPB. MSC delivery normalized both acute and prolonged oxidative/inflammatory insults. At 4 weeks, CPB caused reduced connexin 43 expression and increased cross-sectional area of cardiomyocytes. Consistent with cellular changes, alterations in fractional anisotropy and helix and propagation angles were identified using diffusion tensor imaging 4 weeks post-CPB. Additionally, differential tractography revealed impairments in fiber organization, demonstrating deleterious impacts of CPB on cellular and microstructural maturations of the developing heart. MSC delivery not only mitigated CPB-induced oxidative/inflammatory stresses but also improved cellular and structural impairments following pediatric cardiac surgery.

CPB induces oxidative and inflammatory stresses, thereby causing cellular and structural changes in the developing heart. MSC treatment showed promise in improving CPB-induced impairments of cardiac maturation in neonates and infants undergoing cardiac surgery.