TY - JOUR
T1 - Feasibility of hepatocyte transplantation-based therapies for primary hyperoxalurias
AU - Guha, Chandan
AU - Yamanouchi, Kosho
AU - Jiang, Jinlan
AU - Wang, Xia
AU - Chowdhury, Namita Roy
AU - Santana, Alfredo
AU - Shapiro, Lawrence J.
AU - Salido, Eduardo
AU - Roy-Chowdhury, Jayanta
PY - 2005/3
Y1 - 2005/3
N2 - Primary hyperoxalurias (PHs) are diseases caused by overproduction of oxalate by hepatocytes. Most patients with PHs develop nephrocalcinosis and renal failure. Combined liver-kidney transplantation is often used as a definitive treatment of PHs, but because of a large body oxalate load at the time of transplantation, the procedure is not always successful. Because all hepatocytes overproduce oxalate, partial liver replacement procedures, such as auxiliary transplantation of a liver lobe or hepatocyte transplantation are not expected to be useful in this disorder. In this paper we describe novel techniques, based on preparative hepatic irradiation and stimulation of hepatocyte mitosis, through loss of liver mass or administration of hepatic growth factor, which permit transplanted wild-type hepatocytes to massively repopulatethe liver, replacing up to 90% of the hepatocytes in recipient mouse livers. Application of this procedure in a recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked amelioration of hyperoxaluria. We propose that further refinement of the different components of this procedure may permit early cell-based therapies of PHs, thereby preventing renal failure and its complications.
AB - Primary hyperoxalurias (PHs) are diseases caused by overproduction of oxalate by hepatocytes. Most patients with PHs develop nephrocalcinosis and renal failure. Combined liver-kidney transplantation is often used as a definitive treatment of PHs, but because of a large body oxalate load at the time of transplantation, the procedure is not always successful. Because all hepatocytes overproduce oxalate, partial liver replacement procedures, such as auxiliary transplantation of a liver lobe or hepatocyte transplantation are not expected to be useful in this disorder. In this paper we describe novel techniques, based on preparative hepatic irradiation and stimulation of hepatocyte mitosis, through loss of liver mass or administration of hepatic growth factor, which permit transplanted wild-type hepatocytes to massively repopulatethe liver, replacing up to 90% of the hepatocytes in recipient mouse livers. Application of this procedure in a recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked amelioration of hyperoxaluria. We propose that further refinement of the different components of this procedure may permit early cell-based therapies of PHs, thereby preventing renal failure and its complications.
KW - Fas/CD95
KW - Hepatic growth factor
KW - Hepatic irradiation
KW - Hepatocyte transplantation
KW - Primary hyperoxalurias
UR - http://www.scopus.com/inward/record.url?scp=20844442634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20844442634&partnerID=8YFLogxK
U2 - 10.1159/000085408
DO - 10.1159/000085408
M3 - Article
C2 - 15849463
AN - SCOPUS:20844442634
SN - 0250-8095
VL - 25
SP - 161
EP - 170
JO - American Journal of Nephrology
JF - American Journal of Nephrology
IS - 2
ER -