title: Is xenotransplantation of embryonic stem cells a realistic option?
abstract: To test the purported immune privilege of embryonic stem cells (ESC) in the challenging setting of xenotransplantation, 14 immunocompetent baboons were subjected to a coronary artery occlusion-reperfusion sequence and, two weeks later, randomized to receive in-scar injections of culture medium or cardiac-committed mouse ESC engineered to express fluorescent reporter genes driven by cardiac-specific promoters. Two months after transplantation, left ventricular function, as assessed by echocardiography, deteriorated to a similar extent in control and treated baboons. This correlated with failure to identify the grafted cells by X-gal histology and immunofluorescence. Rejection did not seem to be mediated by xenoantibodies, but rather by T lymphocytes and natural killer cells as suggested by positive immunostaining for CD3 and CD56 early after transplantation. There was no increase in circulating levels of regulatory T cells. These data raise a cautionary note about the immune privilege of ESC and suggest that from a mere immunologic standpoint, ESC xenotransplantation is likely to be an unrealistic challenge.
authors.affiliation: Department of Cardiology, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Bonnevie
authors.forename: Alain
authors.initials: A
authors.lastname: Bel
authors.forename: Laurent
authors.initials: L
authors.lastname: Sabbah
authors.forename: Nawwar
authors.initials: N
authors.lastname: Al Attar
authors.forename: Pascal
authors.initials: P
authors.lastname: Pradeau
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Valérie
authors.initials: V
authors.lastname: Bellamy
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Claudine
authors.initials: C
authors.lastname: Ménard
authors.forename: Michel
authors.initials: M
authors.lastname: Desnos
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Patrice
authors.initials: P
authors.lastname: Binder
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.forename: Michel
authors.initials: M
authors.lastname: Pucéat
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000032:analysis; D004562:Electrocardiography; D053595:Embryonic Stem Cells / Q000276:immunology* / Q000637:transplantation*; D006084:Graft Rejection / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D009203:Myocardial Infarction / Q000601:surgery*; D010215:Papio; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis
chemical_list: D019002:CD56 Antigen