Feasibility of hepatocellular transplantation via the umbilical vein in prenatal and perinatal lambs

Humberto E. Soriano, Alfred L. Gest, Derek K. Bair, Mary VanderStraten, Dorothy E. Lewis, Gretchen J. Darlington, Milton J. Finegold, Fred D. Ledley

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Hepatocellular transplantation has previously been performed in experimental animals by infusion of hepatocyte suspensions into the spleen or portal venous system. Cells injected into these sites flow to the liver and engraft within the hepatic parenchyma. We designed this study to evaluate the feasibility of hepatocellular transplantation through the umbilical vein in the prenatal or perinatal periods. Allogeneic sheep hépatocytes were harvested, stained with the vital fluorescent dye Dil, and injected into the umbilical vein of fetal lambs at 85% gestation and term. Hemodynamic studies performed to assess the physiological impact of transplantation on the recipient animal demonstrated that the procedure was well tolerated. No significant short-term complications were encountered and no lesions were found by conventional histological examination at necropsy 1-17 days after transplantation. Engrafted cells were identified within the liver by fluorescent microscopy and flow cytometry in 4/7 animals constituting 1.2-5% of the hepatocyte population. Fluorescent cellular material with the morphology of hepatocytes, noncellular material, and fluorescent phagocytic cells were seen occasionally in other organs including lung, brain, adrenal, and placenta. These studies demonstrate the feasibility of performing hepatocellular transplantation in the fetus via the umbilical vein in experimental animals.

Original languageEnglish (US)
Pages (from-to)293-304
Number of pages12
JournalFetal Diagnosis and Therapy
Volume8
Issue number5
DOIs
StatePublished - 1993

Keywords

  • Fetal therapy
  • Gene therapy
  • Hepatocellular
  • Transplantation
  • Umbilical vein

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Radiology Nuclear Medicine and imaging
  • Obstetrics and Gynecology

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