Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory responseCentral MessagePerspective
Takuya Maeda, MD, PhD,
Casey M. Briggs, BS,
Anushree Datar, MS,
Christine A. Brantner, PhD,
Patrick J. Hanley, PhD,
Richard A. Jonas, MD,
Nobuyuki Ishibashi, MD
Affiliations
Takuya Maeda, MD, PhD
Center for Neuroscience Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Heart Institute, Children's National Hospital, Washington, DC
Casey M. Briggs, BS
Center for Neuroscience Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Heart Institute, Children's National Hospital, Washington, DC; Virginia Commonwealth University, School of Medicine, Richmond, Va
Anushree Datar, MS
Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC
Christine A. Brantner, PhD
GW Nanofabrication and Imaging Center, The George Washington University School of Medicine and Health Science, Washington, DC
Patrick J. Hanley, PhD
Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC; Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Science, Washington, DC
Richard A. Jonas, MD
Center for Neuroscience Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Heart Institute, Children's National Hospital, Washington, DC
Nobuyuki Ishibashi, MD
Center for Neuroscience Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Heart Institute, Children's National Hospital, Washington, DC; Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Science, Washington, DC; Address for reprints: Nobuyuki Ishibashi, MD, Center for Neuroscience Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Heart Institute, Children's National Hospital, 111 Michigan Ave, NW, Washington, DC 20010-2970.
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 (CPB) 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 120 × 106 mesenchymal stromal cells were injected into the venous reservoir after 80 minutes of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex vivo circulation was maintained for 300 minutes 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 2 groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex vivo CPB conditions. CPB significantly changed the level of interleukin (IL) 4, IL-6, IL-8, IP-10, macrophage colony stimulating factor, macrophage inflammatory protein-1β, monocyte chemoattractant protein-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 CPB during pediatric cardiac surgery.
