Is xenotransplantation of embryonic stem cells a realistic option?
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.
Bonnevie
Lionel
L
Department of Cardiology, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France.
Bel
Alain
A
Sabbah
Laurent
L
Al Attar
Nawwar
N
Pradeau
Pascal
P
Weill
Bernard
B
Le Deist
Françoise
F
Bellamy
Valérie
V
Peyrard
Séverine
S
Ménard
Claudine
C
Desnos
Michel
M
Bruneval
Patrick
P
Binder
Patrice
P
Hagège
Albert A
AA
Pucéat
Michel
M
Menasché
Philippe
P
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
D019002:CD56 Antigen