In utero allotransplantation of fetal hepatocytes in primates.
OBJECTIVE
Because intrauterine transplantation of fetal hepatocytes could become an effective approach for treating severe genetic disorders of the liver, the objective of this study was to demonstrate the feasibility of in utero allotransplantation of fetal hepatocytes in a nonhuman primate model using direct intraparenchymal administration of donor cells.


METHODS
Fetal primary hepatocytes were isolated from 3 fetal primates (MACACA MULATTA) at 89-120 days of gestation, and cryopreserved. When a recipient was available, the cells were thawed and transduced by a beta-galactosidase-expressing retrovirus (3 cases) or labelled with a fluorescent dye (4 cases). Hepatocytes were infused directly into the fetal liver under surgical visual control. Engraftment was assessed by surgical liver biopsies taken 8-60 days following transplantation.


RESULTS
Six recipients survived until liver biopsy, and 1 died during the surgical procedure. There was no evidence of engraftment in the 3 fetuses that received genetically marked hepatocytes. All 3 monkeys who received 20-25 x 10(6) hepatocytes from an 89-day-old donor labelled with fluorescent dye had positive liver biopsies 8-11 days following intrauterine transplantation.


CONCLUSIONS
In utero allotransplantation of fetal hepatocytes is feasible in the nonhuman primate, and direct intraparenchymal administration enables short-term detection of persisting donor hepatocytes.
Mahieu-Caputo
Dominique
D
Equipe mixte, Inserm EMI 0020, Clamart, France. mahieu.caputo@abc.ap-hop-paris.fr
Loux
Nathalie
N
Simon
Lionel
L
Allain
Jean-Etienne
JE
Beaudoin
Sylvie
S
Bargy
Frédéric
F
Andreoletti
Marion
M
Weber
Anne
A
D000818:Animals; D015925:Cryopreservation; D005260:Female; D005315:Fetal Diseases; D005333:Fetus / Q000601:surgery*; D005456:Fluorescent Dyes; D015870:Gene Expression; D005865:Gestational Age; D006085:Graft Survival; D022781:Hepatocytes / Q000637:transplantation*; D008099:Liver / Q000196:embryology*; D008253:Macaca mulatta; D011247:Pregnancy; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014184:Transplantation, Homologous; D001616:beta-Galactosidase / Q000235:genetics
D005456:Fluorescent Dyes; D001616:beta-Galactosidase