Abstract
Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines, such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
| Original language | English |
|---|---|
| Pages (from-to) | 379-387 |
| Number of pages | 9 |
| Journal | Cell Transplantation |
| Volume | 12 |
| Issue number | 4 |
| Publication status | Published - 2003 |
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Keywords
- Allogeneic response
- Gene transfer
- Hepatocyte transplantation
- Viral IL-10
ASJC Scopus subject areas
- Cell Biology
- Transplantation
Cite this
Suppression of allogeneic response by viral IL-10 gene transfer. / Fujisawa, Kenji; Saito, Shinya; Okada, Yutaka; Fujiwara, Toshiyoshi; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki.
In: Cell Transplantation, Vol. 12, No. 4, 2003, p. 379-387.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of allogeneic response by viral IL-10 gene transfer
AU - Fujisawa, Kenji
AU - Saito, Shinya
AU - Okada, Yutaka
AU - Fujiwara, Toshiyoshi
AU - Yagi, Takahito
AU - Iwagaki, Hiromi
AU - Tanaka, Noriaki
PY - 2003
Y1 - 2003
N2 - Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines, such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
AB - Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines, such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
KW - Allogeneic response
KW - Gene transfer
KW - Hepatocyte transplantation
KW - Viral IL-10
UR - http://www.scopus.com/inward/record.url?scp=0043210582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0043210582&partnerID=8YFLogxK
M3 - Article
C2 - 12911125
AN - SCOPUS:0043210582
VL - 12
SP - 379
EP - 387
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 4
ER -