1993 Fiscal Year Final Research Report Summary
Basic and clinical research of selective transplantation for metabolic support and modulation of graft-immunogenecity.
| Project/Area Number |
02404050
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Asahikawa Medical College |
|---|
Principal Investigator |
MITO Michio Asahikawa Medical College, Vice President, 副学長 (60000981)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INAGAKI Mitsuhiro Asahikawa Medical College, Fellow, 医学部, 助手 (80261410)
SAKATA Hiromi Asahikawa Medical College, Fellow, 医学部, 助手 (50235157)
ONODERA Kazuhiko Asahikawa Medical College, Fellow, 医学部, 助手 (00204264)
KUSANO Mitsui Asahikawa Medical College, Associate Professor, 医学部, 講師 (70091569)
KASAI Shinichi Asahikawa Medical College, Associate Professor, 医学部, 助教授 (40091566)
|
|---|
| Project Period (FY) |
1990 – 1993
|
| Keywords | Hepatocyte transplantation / Intrasplenic transplantation / Monoclonal antibody / Hepatocyte growth factor / Cryopreservation / Human hepatocyte / Electroporation / Retrovirus-vector |
|---|
| Research Abstract |
The advantages of cellular transplantation are : 1) requires no vascular anastomosis, 2) autotransplantation is applicable, 3) complicated and hazardous immunosuppressive drugs are not necessary with autotransplantation, 4) long-term cryopreservation is possible, and 5) gene therapy is easily applied.
Our success with long survival of transplantated rat and monkey hepatocytes in the spleen and development of a preparation of isolated human hepatocytes has renewed interests in clinical trials of hepatocyte transplantation (HCTX). In several cases, we have observed the fate of human hepatocytes in the spleen for a long period. So far, we detected inoculated hepatocytes in the spleen, but there little evidence that inoculated hepatocytes can proliferate and occupy the large area of the spleen in man.
In basic experiments, we evaluated the beneficial effects of exogenous growth factors on proliferation of inoculated hepatocytes in the spleen and immuno-modulation using monoclonal antibodies for cell-surface antigens. And also, advances in gene-engineering enable us to do exogenous gene-transfer to isolated hepatocytes by electroporation and retrovirus-vector. Gene transfection and subsequent HCTX need to be promotion, but several fundamental problems remain unresolved : 1) whether or not human hepatocytes can proliferate in vivo, and if proliferate, how long do inoculated hepatocytes maintain their hepatic function? , 2) where is the most suitable inoculation site? , and 3) development of the method for exogenous gene-transfection into human hepatocytes and control of the expression leve of transfected gene in hepatocytes.
Basic experiments to solve these problems must be accelerated fully, and HCTX with geneengineering will become one choice of the treatments for liver diseases.
|
Research Products
(15 results)
