Abstract
Background: Hepatocyte transplantation is an attractive potential treatment for liver-based inborn
errors of metabolism and for fulminant hepatic failure. Dalmatian dogs have a metabolic
error that results in hyperuricosuria. This report focuses on the effect of multiple,
sequential intrasplenic transplants of fresh and cryopreserved hepatocytes in dalmatians.
Methods: Dalmatians underwent intrasplenic hepatocyte transplantation with hepatocytes taken
from healthy mongrels. Dalmatian urinary uric acid excretion was measured preoperatively,
and this served as the control value. Three hepatocyte transplantations were performed
at 30-day intervals—the first with freshly isolated cells,and both the second and
the third with cryopreserved hepatocytes from the same donor. Urinary uric acid excretion
was measured postoperatively twice per week. Results: The urinary uric acid excretion decreased an average of 54% after the first hepatocyte
transplantation. The effect was transient and lasted an average of 22 days (range,
19-50 days). Subsequent intrasplenic hepatocyte transplantation with cryopreserved
hepatocytes resulted in similar decreases in urinary uric acid excretion. Each transplant
resulted in a significant decrease in urinary uric acid excretion when compared with
baseline values (P = <.001). Conclusions: Sequential intrasplenic hepatocyte transplantation is feasible in this model. This
method provided a significant, but transient, correction in urinary uric acid excretion
that was similar with either fresh or cryopreserved hepatocytes. A substantial biologic
effect provided by cryopreserved hepatocytes has important implications in clinical
hepatocyte transplantation. (Surgery 2000;127:193-9.)
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References
- Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.Transplantation. 1997; 63: 559-569
- Human hepatocyte transplantation: gene therapy and more?.Pediatrics. 1998; 102: 647-648
- Hepatocyte transplantation in man.Cell Transplant. 1993; 2: 65-74
- A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia.Nat Med. 1995; : 1148-1154
- Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation.N Engl J Med. 1998; 338: 1422-1426
- Human fetal hepatocyte transplantation in patients with fulminant hepatic failure.Transplantation. 1994; 58: 951-952
- Uric acid metabolism in Dalmatians and other dogs: Role of the liver.Arch Intern Med. 1972; 129: 492
- Low uricase activity in the Dalmatian dog simulated in mongrels given oxonic acid.Am J Phys. 1971; 220: 973-979
- Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits.Science. 1991; 254: 1802-1805
- Hepatocellular transplantation for metabolic deficiencies: decrease of plasma bilirubin in Gunn rats.Science. 1976; 192: 892-894
- Selective intraportal hepatocyte transplantation in analbuminemic and Gunn rats.Transplantation. 1993; 55: 1213-1219
- Intra-splenic hepatocyte allotransplantation in Dalmatian dogs with and without CSA immunosuppression.Transplantation. 1997; 63: 1206-1209
- Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model.Transplantation. 1996; 62: 358-364
- Large-scale cryopreservation of isolated dog hepatocytes.Cryobiology. 1993; 30: 1-11
- Viability and function in primary culture of adult hepatocytes from various animal species and human beings after cryopreservation.Hepatology. 1993; 18: 406-414
- Morphology and function of isolated hepatocytes transplanted into rat spleen.Transplantation. 1979; 28: 499-505
- Transcatheter hepatocyte transplantation: Pre-clinical studies of anatomic consequences in the portal vascular bed.Acad Radiol. 1994; 1: 229-236
- Observations on rat spleen reticulum during the development of syngeneic hepatocellular implants.Br J Exp Pathol. 1986; 67: 329-339
- Transplantation of hepatocytes; an in-vitro and in-vivo study in canines.Cell Transplant. 1994; 3: 193-201
- Evidence that temporary complete occlusion of splenic vessels prevents massive embolization and sudden death associated with IS hepatocellular transplantation.Transplantation. 1989; 47: 449-450
- Studies on the safety of intrasplenic hepatocyte transplantation: relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure.Hum Gen Ther. 1993; 4: 249-257
- Historical review of hepatocyte transplantation: The road from whole liver transplantation to hepatocyte transplantation.in: Hepatocyte transplantation. Kareger Lander Systems, Basel1997: 4-5
- Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirubinemia.J Pediatr Surg. 1992; 27: 298-301
- Observations on initial cell loss after intraportal hepatocyte transplantation of 5'-bromo-deoxy-uridine-labeled hepatocytes.Eur Surg Res. 1997; 29: 411-420
- Liver regeneration utilizing isolated hepatocytes transplanted into the rat spleen.Surg Forum. 1978; 29: 338-340
- 111Indium labeling of hepatocytes for analysis of short-term biodistribution of transplanted cells.Hepatology. 1994; 19: 750-757
Article info
Publication history
Accepted:
July 28,
1999
Footnotes
*Supported in part by the Eleanor B. Pillsbury Foundation.
**Reprint requests: Enrico Benedetti, MD, Division of Transplantation, University of Illinois at Chicago, 840 S Wood St M/C 958, Chicago, IL 60612.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.