In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: Feasibility and short-term follow-up

In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing β-galactosidase. Transduction efficiency was 75–85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1–2 107 transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3–4 107 hepatocytes by direct intrahepatic injection. All the fetuses survived without side ef...