Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations

Overview

Human splenic physiology remains poorly understood due to lack of functional exploration. However, through its ability to recognize alterations or modifications in circulating cells and to trigger an innate and adaptive response in response to these anomalies, the spleen plays a central role in several diseases affecting blood cells, directly or indirectly. The analysis of the splenic clearance of abnormal cells during ex-vivo perfusions made it possible to clarify the pathogenesis of malaria and the role of the spleen in the adaptive immune response. The study's investigative team wishes to extend these explorations to other human diseases in which the spleen is involved, and to evaluate the preventive or curative potential of substances that can modify the perception of blood cells by the spleen (e.g. monoclonal antibodies directed against circulating cells, among other options).

Human splenic physiology remains poorly understood due to lack of functional exploration. However, through its ability to recognize alterations or modifications in circulating cells and to trigger an innate and adaptive response in response to these anomalies, the spleen plays a central role in several diseases affecting blood cells, directly or indirectly. The analysis of the splenic clearance of abnormal cells during ex-vivo perfusions made it possible to clarify the pathogenesis of malaria and the role of the spleen in the adaptive immune response. The study's investigative team wishes to extend these explorations to other human diseases in which the spleen is involved, and to evaluate the preventive or curative potential of substances that can modify the perception of blood cells by the spleen (e.g. monoclonal antibodies directed against circulating cells, among other options). Participation to the study will be proposed to adult patients in whom a splenic intervention (spleno-pancreatectomy, or a total or partial splenectomy) is planned as part of their treatment. One or more tubes of venous blood collected for the care will be retrieved following the pre- or intra-operative assessment. These samples will serve as controls during analyzes of splenic filtration mechanisms and/or perfusion experiments with populations of altered or modified cells and/or immunological and/or genetic analyses. Immediately following surgery, after careful examination by the pathologist in charge, the whole spleen or spleen fragments will be collected for further analysis. Whenever possible a catheter will be introduced in the splenic artery, the spleen will be flushed/rinsed with 0.1 - 2 L of cold perfusion medium then transferred to the laboratory for ex-vivo perfusion. Samples from different experimental conditions (for example red blood cell containing malaria parasite for a culture) may be introduced in the perfusion system pour kinetic analyses. Before and at the end of the ex-vivo perfusion, splenic blood and spleen fragments will be collected and processed for further analyses by cytology, cytometry, histology, immunohistochemistry, electronic microscopy, biochemistry, molecular biology, single cell analyses, on any other method. Peripheral and splenic blood samples or cells, as well as spleen fragments will be stored in. a biobank for further use or experimental analyses.