Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

Abstract Objective Mesenchymal stromal cells have important immunomodulatory and neuroprotective properties. The aim of this study was to evaluate the feasibility of mesenchymal stromal cell administration into a cardiopulmonary bypass circuit including a pediatric oxygenator, and to assess the immunomodulatory response of the circulating blood prime. Methods A bypass circuit with a pediatric oxygenator including integral filter was primed with bank whole blood. Normal saline (control) or 120x106 mesenchymal stromal cells were injected into the venous reservoir after 80min of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex-vivo circulation was maintained for 300min after administration. Results There were no differences in flow rate, trans-oxygenator pressure gradient, blood oxygen and carbon dioxide levels between control and cell delivery groups. No adhesion of mesenchymal stromal cells was observed on the filter mesh by scanning electron microscopy. Lymphocyte surface marker assay found no difference in the number of B cells, T cells, or natural killer cells between the two groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex-vivo cardiopulmonary bypass conditions. Cardiopulmonary bypass significantly changed the level of IL-4, IL-6, IL-8, IP-10, GM-CSF, MIP-1β, MCP-1, and IL-1α over time. IL-6 level was significantly increased after cell administration. Conclusions The administration of mesenchymal stromal cells does not interfere with oxygenator function. Allogeneic mesenchymal stromal cells show no immunogenicity, and increase plasma IL-6 level during ex-vivo circulation. Further investigation is necessary to determine the effect of mesenchymal stromal cell delivery through cardiopulmonary bypass during pediatric cardiac surgery.