Vascular grafts are used in congenital heart defect corrective surgery. However, these grafts have limited durability and often require repeat operations because of the lack of growth potential. Tissue engineering has the promise to produce a graft with growing/remodelling/repairing capacity. We are developing CorMatrix extracellular matrix (ECM) vascular grafts seeded with piglet peripheral blood-derived mesenchymal stem cells (pbMSC) and testing them in the left pulmonary artery of another piglet. This study aims at investigating whether seeding the grafts with stem cells from a donor piglet causes an adverse immune response in the receiver piglet. Five-weeks old piglets (11 kg) were operated using standardised anaesthetic (ketamine/isoflurane) and surgical (left thoracotomy/anastomosis) protocols in accordance with UK home office guidance (Project Licence no PPL30/3019). Three animal groups were compared. In the first, the pigs did not undergo an operation. In the second, acellular porcine small intestine sub-mucosa (SIS) was implanted (unseeded). In the third, MSCs isolated from blood were seeded onto the SIS, grown in a bioreactor and implanted (seeded). Cell-seeded and unseeded scaffolds were shaped into conduits and implanted in the left pulmonary artery of piglets. Six months following surgery, echocardiography was carried-out and grafts were harvested and analysed by histology. The spleen, an important organ of the immune system, was taken from the pigs and analysed for inflammatory markers using qPCR and immunostaining. The inflammatory cytokines TNF-alpha and interleukin 10 (IL-10) were measured by qPCR. And the expression of major histocompatibility complex II (MHC II) was measured by immunostaining. Six months post-operatively, ultrasound data demonstrated that the unseeded and seeded grafts were patent. Histology showed graft integration within the left pulmonary artery. The expression of inflammatory markers, TNF-alpha and IL-10, was similar across all groups. The MHC II expression seemed slightly lower in the seeded group compared to the non-operated and unseeded group. These results suggest that implanting grafts seeded with donor piglet blood MSC does not cause any excessive or adverse immune responses in the receiver piglet. The lower expression of MHC II in the spleen of cell-seeded group animals suggests that perhaps MSCs help modulate inflammation following this procedure.