title: Ex vivo perfusion of human spleens maintains clearing and processing functions.
abstract: The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation--left splenopancreatectomy for benign pancreas tumors--allowing spleen retrieval at no risk for patients. Ex vivo perfusion of retrieved intact spleens for 4 to 6 hours maintained a preserved parenchymal structure, vascular flow, and metabolic activity. Function preservation was assessed by testing the ability of isolated-perfused spleens to retain Plasmodium falciparum-infected erythrocytes preexposed to the antimalarial drug artesunate (Art-iRBCs). More than 95% of Art-iRBCs were cleared from the perfusate in 2 hours. At each transit through isolated-perfused spleens, parasite remnants were removed from 0.2% to 0.23% of Art-iRBCs, a proportion consistent with the 0.02% to 1% pitting rate previously established in artesunate-treated patients. Histologic analysis showed that more than 90% of Art-iRBCs were retained and processed in the red pulp, providing the first direct evidence of a zone-dependent parasite clearance by the human spleen. Human-specific physiologic or pathophysiologic mechanisms involving clearing or processing functions of the spleen can now be experimentally explored in a human tissue context.
authors.affiliation: Biomedical Research Team, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France. pabuffet@pasteur.fr
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Valentine
authors.initials: V
authors.lastname: Brousse
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Correas
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dousset
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Reza
authors.initials: R
authors.lastname: Kianmanesh
authors.forename: Olivier
authors.initials: O
authors.lastname: Farges
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: François
authors.initials: F
authors.lastname: Paye
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Ungeheuer
authors.forename: Catherine
authors.initials: C
authors.lastname: Ottone
authors.forename: Huot
authors.initials: H
authors.lastname: Khun
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Guigon
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000469:parasitology / Q000503:physiopathology; D010477:Perfusion; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity; D012717:Sesquiterpenes / Q000494:pharmacology; D013154:Spleen / Q000098:blood supply / Q000276:immunology / Q000469:parasitology / Q000502:physiology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate