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Original Communications| Volume 127, ISSUE 2, P193-199, February 2000

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Multiple intrasplenic hepatocyte transplantations in the dalmatian dog

      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

        • Strom SC
        • Fisher RA
        • Thompson MT
        • Sanyal AJ
        • Cole PE
        • Ham JM
        • et al.
        Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.
        Transplantation. 1997; 63: 559-569
        • Chowdhury JR
        • Chowdhury NR
        • Strom SC
        • Kaufman SS
        • Horslen S
        • Fox IJ
        Human hepatocyte transplantation: gene therapy and more?.
        Pediatrics. 1998; 102: 647-648
        • Mito M
        • Kusano M
        Hepatocyte transplantation in man.
        Cell Transplant. 1993; 2: 65-74
        • Grossman M
        • Rader DJ
        • Muller DW
        • Kolansky DM
        • Kozarsky K
        • Clark III, BJ
        • et al.
        A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia.
        Nat Med. 1995; : 1148-1154
        • Fox IJ
        • Chowdhury JR
        • Kaufman SS
        • Goertzen TC
        • Chowdhury NR
        • Warkentin PI
        • et al.
        Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation.
        N Engl J Med. 1998; 338: 1422-1426
        • Habibullah CM
        • Syed IH
        • Qamar A
        • Taher-Uz A
        Human fetal hepatocyte transplantation in patients with fulminant hepatic failure.
        Transplantation. 1994; 58: 951-952
        • Kuster G
        • Shorter R
        • Dawson B
        • Hallenbeck GA
        Uric acid metabolism in Dalmatians and other dogs: Role of the liver.
        Arch Intern Med. 1972; 129: 492
        • Yu TF
        • Gutman AB
        • Berger L
        • Kaung C
        Low uricase activity in the Dalmatian dog simulated in mongrels given oxonic acid.
        Am J Phys. 1971; 220: 973-979
        • Chowdhury JR
        • Grossman M
        • Gupta S
        • Chowdhury NR
        • Baker JR
        • Wilson JM
        Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits.
        Science. 1991; 254: 1802-1805
        • Matas AJ
        • Sutherland DE
        • Steffes MW
        • Mauer SM
        • Sowe A
        • Simmons RL
        • et al.
        Hepatocellular transplantation for metabolic deficiencies: decrease of plasma bilirubin in Gunn rats.
        Science. 1976; 192: 892-894
        • Holzman MD
        • Rozga J
        • Neuzil DF
        • Griffin D
        • Moscioni AD
        • Demetriou AA
        Selective intraportal hepatocyte transplantation in analbuminemic and Gunn rats.
        Transplantation. 1993; 55: 1213-1219
        • Benedetti E
        • Kirby JP
        • Asolati M
        • Blanchard J
        • Ward MG
        • Williams R
        • et al.
        Intra-splenic hepatocyte allotransplantation in Dalmatian dogs with and without CSA immunosuppression.
        Transplantation. 1997; 63: 1206-1209
        • Kocken JM
        • Borel Rinkes IH
        • Bijma AM
        • de Roos WK
        • Bouwman E
        • Terpstra OT
        Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model.
        Transplantation. 1996; 62: 358-364
        • Kasai S
        • Mito M
        Large-scale cryopreservation of isolated dog hepatocytes.
        Cryobiology. 1993; 30: 1-11
        • Chesne C
        • Guyomard C
        • Fautrel A
        • Poullain MG
        • Fremond B
        • De Jong H
        • et al.
        Viability and function in primary culture of adult hepatocytes from various animal species and human beings after cryopreservation.
        Hepatology. 1993; 18: 406-414
        • Mito M
        • Ebata H
        • Kusano M
        • Onishi T
        • Saito T
        • Sakamoto S
        Morphology and function of isolated hepatocytes transplanted into rat spleen.
        Transplantation. 1979; 28: 499-505
        • Kerr A
        • Rajvanshi P
        • Gupta S
        Transcatheter hepatocyte transplantation: Pre-clinical studies of anatomic consequences in the portal vascular bed.
        Acad Radiol. 1994; 1: 229-236
        • Darby H
        • Gupta S
        • Johnstone R
        • Selden AC
        • Hodgson HJF
        Observations on rat spleen reticulum during the development of syngeneic hepatocellular implants.
        Br J Exp Pathol. 1986; 67: 329-339
        • Rivas PA
        • Fabrega AJ
        • Schwartz D
        • Dagiantis W
        • Ward MG
        • Blanchard J
        • et al.
        Transplantation of hepatocytes; an in-vitro and in-vivo study in canines.
        Cell Transplant. 1994; 3: 193-201
        • Nieto JA
        • Escandon J
        • Betancor C
        • Ramos J
        • Canton T
        • Cuervas-Mons V
        Evidence that temporary complete occlusion of splenic vessels prevents massive embolization and sudden death associated with IS hepatocellular transplantation.
        Transplantation. 1989; 47: 449-450
        • Gupta S
        • Yerneni P
        • Vemuru RP
        • Lee CD
        • Yellin EL
        • Bhargava KK
        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
        • Mito M
        • Sawa M
        Historical review of hepatocyte transplantation: The road from whole liver transplantation to hepatocyte transplantation.
        in: Hepatocyte transplantation. Kareger Lander Systems, Basel1997: 4-5
        • Asonuma K
        • Gilbert JC
        • Stein JE
        • Takeda T
        • Vacanti JP
        Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirubinemia.
        J Pediatr Surg. 1992; 27: 298-301
        • Kocken JM
        • Bouwman E
        • Borel Rinkes IH
        • Sinaasappel M
        • Terpstra OT
        Observations on initial cell loss after intraportal hepatocyte transplantation of 5'-bromo-deoxy-uridine-labeled hepatocytes.
        Eur Surg Res. 1997; 29: 411-420
        • Ebata H
        • Kusano M
        • Onishi T
        • Saito T
        • Mito M
        Liver regeneration utilizing isolated hepatocytes transplanted into the rat spleen.
        Surg Forum. 1978; 29: 338-340
        • Gupta S
        • Lee C
        • Vemuru RP
        • Bhargava KK
        111Indium labeling of hepatocytes for analysis of short-term biodistribution of transplanted cells.
        Hepatology. 1994; 19: 750-757