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

被引:21
作者
Cusick, RA
Lee, HM
Sano, KR
Pollok, JM
Utsunomiya, H
Ma, PX
Langer, R
Vacanti, JP
机构
[1] CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115
[2] HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA
[3] MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139
关键词
fetal hepatocytes; tissue engineering; hepatocyte transplantation;
D O I
10.1016/S0022-3468(97)90210-4
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 oi fetal dells 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&E), and the cell area of each specimen (24 sections per group) was quantitated using morphometric analysis. Results were statistically analysed 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 10(5) mu m(2); fetal cells into adults, 0.47 x 10(5) mu m(2); adult into 4-week neonates, 1.17 x 10(5) mu m(2); fetal into 4-week neonates, 4.54 x 10(5) mu m(2); adult into 2-week neonates, 2.98 x 10(5) mu m(2), and fetal into a-week neonates; 5.81 x 10(5) mu m(2). 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. Copyright (C) 1997 by W.B. Saunders Company.
引用
收藏
页码:357 / 360
页数:4
相关论文
共 13 条
[1]   STUDIES IN RAT-LIVER PERFUSION FOR OPTIMAL HARVEST OF HEPATOCYTES [J].
AIKEN, J ;
CIMA, L ;
SCHLOO, B ;
MOONEY, D ;
JOHNSON, L ;
LANGER, R ;
VACANTI, JP .
JOURNAL OF PEDIATRIC SURGERY, 1990, 25 (01) :140-145
[2]  
*AM LIV FDN, 1988, VIT STAT US A, V2
[3]   QUANTITATION OF TRANSPLANTED HEPATIC MASS NECESSARY TO CURE THE GUNN RAT MODEL OF HYPERBILIRUBINEMIA [J].
ASONUMA, K ;
GILBERT, JC ;
STEIN, JE ;
TAKEDA, T ;
VACANTI, JP .
JOURNAL OF PEDIATRIC SURGERY, 1992, 27 (03) :298-301
[4]  
CUSICK RA, 1995, SURG FORUM, V40, P658
[5]   TISSUE ENGINEERING [J].
LANGER, R ;
VACANTI, JP .
SCIENCE, 1993, 260 (5110) :920-926
[6]  
MARCEAU N, 1982, IN VITRO CELL DEV B, V18, P1
[7]   Autocrine angiogenic vascular prosthesis with bone marrow transplantation [J].
Noishiki, Y ;
Tomizawa, Y ;
Yamane, Y ;
Matsumoto, A .
NATURE MEDICINE, 1996, 2 (01) :90-93
[8]   Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia [J].
Raper, SE ;
Grossman, M ;
Rader, DJ ;
Thoene, JG ;
Clark, BJ ;
Kolansky, DM ;
Muller, DWM ;
Wilson, JM .
ANNALS OF SURGERY, 1996, 223 (02) :116-126
[9]  
*SERV ADM, 1994 ANN REP US SCI, pG16
[10]  
SIGAL SH, 1994, HEPATOLOGY, V19, P999