期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 158, 期 2, 页码 771-777出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0002-9440(10)64019-9
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资金
- NIDDK NIH HHS [P30 DK041296, R01 DK017609, R01 DK17609, P30 DK41296] Funding Source: Medline
- Telethon [A.110] Funding Source: Medline
A strategy for hepatocyte transplantation was recently developed whereby massive replacement of the recipient liver is achieved after a combined treatment with retrorsine, a pyrrolizidine alkaloid, and partial hepatectomy, We now investigated whether liver repopulation could occur in this animal model in the absence of any exogenous growth stimuli (eg, partial hepatectomy) for the transplanted cells. Dipeptidyl-peptidase type IV-deficient (DPPIV-) rats were used as recipients. Rats were given two injections of retrorsine (30 mg/kg each, 2 weeks apart), followed by transplantation of 2 x 10(6) hepatocytes isolated from a normal, syngeneic, DPPIV+ donor. At 2 weeks after transplantation, clusters of DPPIV+ hepatocytes occupied 3.3 +/- 0.9% of host liver, increasing to 38.2 +/- 6.3% at 2 months, acid to 65.9 +/- 8.8% at 5 months. By 1 year, >95% of the original hepatocytes were replaced by donor-derived cells. Serum parameters related both to hepatocyte function and integrity (including glucose, bilirubin, total proteins, cholinesterase, alanine aminotransferase, and alkaline phosphatase) were in the normal range in rorsine-treated and repopulated animals. These results provide further insights toward developing strategies for effective liver repopulation by transplanted hepatocytes with reduced toxicity for the host acid potential clinical applicability.
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