(P002) ALLOGENIC RECELLULARIZATION OF BOVINE PERICARDIUM USING HUMAN MESENCHYMAL STEM CELLS REDUCES IMMUNE MEDIATED REJECTION AGAINST XENOGENIC TISSUES

Background: Bioprosthetic heart valves (BHV) undergo time and age-dependent structural valve deterioration (SVD). Prior research has shown that SVD is mediated by an immune-mediated rejection process. Tissue-engineered heart valves (TEHV) have been created to attenuate this immune rejection by removing xenogenic cells from the BHV followed by recellularizing the scaffold with mesenchymal stem cells (MSC). This study presents evidence that TEHV recellularized with allogenic human MSCs can attenuate hyperacute and acute immune rejection.

METHODS AND RESULTS: Bovine pericardium (BP) tissue sections underwent our decellularization protocol and were recellularized with allogenic human MSCs. Native untreated BP (NBP), decellularized BP (DBP), and recellularized BP (RBP)with allogeneic MSCs were used as treatment groups, while autogenic human pericardium (HP) served as a negative control group. Each group was exposed to whole blood obtained from the patient undergoing cardiac surgery. Blood samples were collected at 2 hours and 3 days post-exposure to assess for hyperacute and acute immune reactions respectively.

Hyperacute rejection was tested with a c5a complement protein on ELISA, and RBP and HP showed a decreased trend when compared to NBP and DBP. Acute rejection was tested with proinflammatory cytokines TNF-α, IL-1β, IL-6, IFN-y, and IL-12p40 on ELISA, which showed decreased trends of cytokine presence on RBP and HP when compared to NBP and DBP. Increased proteolytic activity as evidenced by increased MMP9 and decreased TIMP1 and TIMP2 on ELISA was seen on NBP and DBP when compared to RBP and HP.

Conclusion: Our data suggests allogenic MSC recellularization of decellularized bovine pericardium can reduce hyperacute rejection, acute rejection, and proteolytic activity when exposed to human whole blood.