Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine
Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine
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DOI：
10.1016/s0002-9440(10)64019-9
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发表时间：
2001-02-01
影响因子：
6
通讯作者：
Laconi, E
中科院分区：
文献类型：
--
作者：
Laconi, S;Pillai, S;Laconi, E
最近发展了一种肝细胞移植策略，在逆转录酶、吡咯利西啶生物碱和部分肝切除术联合治疗后，可以实现受体肝脏的大量替代。我们现在研究了在没有任何外源性生长刺激（例如，部分肝切除术）的情况下，移植细胞是否可以在这种动物模型中发生肝脏再生。二肽基肽酶iv型缺陷（DPPIV-）大鼠作为受体。给大鼠注射两次逆转录酶（每次30 mg/kg，间隔2周），然后移植从正常、同基因、DPPIV+供体分离的2 × 10(6)个肝细胞。移植后2周，DPPIV+肝细胞簇占宿主肝脏的3.3 +/- 0.9%，2个月时增加到38.2 +/- 6.3%，5个月时增加到65.9 +/- 8.8%。1年后，95%的原始肝细胞被供体来源的细胞所取代。与肝细胞功能和完整性相关的血清参数（包括葡萄糖、胆红素、总蛋白、胆碱酯酶、丙氨酸转氨酶和碱性磷酸酶）在罗辛处理和重新填充的动物中处于正常范围。这些结果为开发有效的移植肝细胞肝脏再生策略提供了进一步的见解，降低了宿主酸的毒性，具有潜在的临床适用性。
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.