The effect of donor and recipient age on engraftment of tissue- engineered liver

Robert A. Cusick, Hanmin Lee, Kaoru Sano, Joerg M. Pollok, Hirofumi Utsunomiya, Peter X. Ma, Robert Langer, Joseph P. Vacanti

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

A novel treatment for end-stage liver disease using heterotopic hepatocyte transplantation on biodegradable polymers has been investigated. Survival and repopulation of adequate cell mass to replace hepatic function has been the principal difficulty of this method. Hence the authors have begun to investigate the role of donor and recipient age on the efficiency of hepatocyte transplantation. Lewis rats were used as donors and recipients. Hepatocytes were isolated with a collagenase digestion, both for the adult and fetal livers (17 days estimated gestational age). After digestion, the hepatocytes were seeded onto 95% porous poly-(L)lactic acid matrices. The polymer-cell constructs with adult or fetal cells were then implanted between mesenteric leaves of three different recipient groups: adults (approximately 200 g), 2-week, and 4-week neonates (two to five animals per group, depending on litter size). The specimens were harvested at 4 weeks, stained with Hematoxylin and Eosin (H and E), and the cell area of each specimen (24 sections per group) was quantitated using morphometric analysis. Results were statistically analyzed using an unpaired, two-tailed Student's t test. At 4 weeks, all specimens showed survival of groups of hepatocytes, especially along the periphery of the polymers and near blood vessels. The hepatocyte cell area for the six groups was calculated in square micrometers: the adult cells transplanted into adult recipients, 0.16 x 105 μm2; fetal cells into adults, 0.47 x 105 μm2; adult into 4-week neonates, 1.17 x 105 μm2; fetal into 4-week neonates, 4.54 x 105 μm2; adult into 2-week neonates, 2.98 x 105 μm2, and fetal into 2-week neonates, 5.81 x 105 μm2. In all three recipient groups, the area of fetal hepatocytes was approximately two to three times the area of the adult hepatocytes (P < .05 for 2-week and 4- week neonatal recipients, P = .06 for adult recipients). Also, as the recipient age decreased, there was an increase in the hepatocyte cell area (P < .05 for fetal or adult groups). The authors conclude that fetal hepatocytes heterotopically transplanted have a significant survival advantage over adult hepatocytes, independent of recipient age. The authors further conclude that the neonatal environment is more favorable than the adult environment for implantation of hepatocytes.

Original languageEnglish (US)
Pages (from-to)357-360
Number of pages4
JournalJournal of pediatric surgery
Volume32
Issue number2
DOIs
StatePublished - Feb 1997

Keywords

  • Fetal hepatocytes
  • hepatocyte transplantation
  • tissue engineering

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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    Cusick, R. A., Lee, H., Sano, K., Pollok, J. M., Utsunomiya, H., Ma, P. X., Langer, R., & Vacanti, J. P. (1997). The effect of donor and recipient age on engraftment of tissue- engineered liver. Journal of pediatric surgery, 32(2), 357-360. https://doi.org/10.1016/S0022-3468(97)90210-4