1995 Fiscal Year Final Research Report Summary
EFFECT OF HEPATOCELLULAR TRANSPLANTATION VIA UMBICAL VEIN IN FETAL RATS OF CONGENITAL METABOLIC DISEASE
| Project/Area Number |
06671175
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
KATO Kazuya Asahikawa Medical College, Assistant Professor, 医学部, 講師 (70175280)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Masato Asahikawa Medical College, Assistant, 医学部, 助手 (10271769)
INAGAKI Mitsuhiro Asahikawa Medical College, Assistant, 医学部, 助手 (80261410)
YAMAMOTO Tetsu Asahikawa Medical College, Assistant Professor, 医学部, 講師 (50125415)
KASAI Shinichi Asahikawa Medical College, Assistant Professor, 医学部, 助教授 (40091566)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Hepatocyte Transplantation / Congenital enzyme deficiency / Intra hepatic fetal liver tissue transplantation / ODS rat / Intrasplenically fetal hepatocyte transplantation / Cytochrome P450 |
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| Research Abstract |
Prenatal treatment is needed for inherited liver enzyme deficiency which occurs and progresses at parental period. We studied effects of prenatal hepatocellular transplantation by infusion of hepatocytes via the umbilical vein, using ODS-^<od>/od rat, which is a mutant unable to synthesize ascorbic acid (AsA) in the liver because of a lack of L-gulonolactone oxidase in the liver microsomes. And also we studied the expression of cytochromes P450 of fetal hepatocyte transplanted into adult SHR spleen syngenitically. I : Hepatocytes were isolated from ODS-^+/+ rat, which is congeneic to ODS-^<od>/od but can synthesize AsA.Laparotomy was performed on female ODS-^<od>/od rats at 18 days of gestation, and uterus wall above one of the fetuses was fixed to abdominal wall. After small incision was added to the uterus wall and anmion, umbilical cord was drawn out and 2-4x10^5 hepatocytes were infused to the umbilical vein by 30 gauge needle under microscopy. Rats were fed a standard diet contain
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ing AsA for 6 weeks after operation. Out of 6 recipients which were born alive and survived for 6 weeks, 2 rats showed late onset of disease and survived twice as long as controls after the cessation of AsA administration. This effect is thought to be derived from hepatocytes implanted in the liver of recipient. II : Fetal hepatocytes were harvested at 20 days of gestation from spontaneously hypertensive rats (SHR) and then transplanted into recipient adult SHR spleens. Morphological examination of the recipient spleens revealed that after 6 weeks, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Of major significance was the fact that hepatocyte transplanted spleens were able to express several families of cytochrome P450 proteins 2-10 weeks after transplantation. Thus, the transplanted hepatocyte tissue appeared to grow and develop a cytochrome P450 metabolic system. This therapy might be of great advantage for repeated allogeneic hepatocyte transplantation, if immunological tolerance is induced at prenatal period. Less
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