Weber Anne, Groyer-Picard Marie-Thérèse, Dagher Ibrahim
Hôpital de Bicêtre, Inserm U 804; University Paris-Sud, Clamart, Kremlin-Bicêtre, France.
Methods Mol Biol. 2009;481:83-96. doi: 10.1007/978-1-59745-201-4_8.
The poor hepatocyte engraftment efficiency and the low level of their expansion in the host liver are a major limitation to cell therapy for the treatment of life-threatening liver diseases. Many rodent models have shown that liver repopulation via transplanted hepatocytes occurs only when liver growth capacity is impaired for an extended period of time. However, these models are not transposable to the clinics and to date there is no safe method to achieve this result in a clinical setting.Therefore, it is necessary to define on large animal models strategies that provide to transplanted hepatocytes sufficient proliferation stimuli to induce their division and that could permit a direct extrapolation to humans. Such procedures should be transposable to patients. We have defined a protocol of liver partial portal branch embolisation and shown that it induces the proliferation of transplanted hepatocytes in non-human primates (Macaca mulatta). This animal model is also appropriate to evaluate the lentiviral-mediated ex vivo gene therapy approach, since simian hepatocytes are efficiently transduced by HIV-1-derived lentivirus vectors.
肝细胞在宿主体内的低植入效率及其在肝脏中的低增殖水平是危及生命的肝脏疾病细胞治疗的主要限制因素。许多啮齿动物模型表明，只有当肝脏生长能力长期受损时，移植的肝细胞才会发生肝脏再填充。然而，这些模型无法直接应用于临床，迄今为止，尚无在临床环境中实现这一结果的安全方法。因此，有必要在大型动物模型上确定一些策略，为移植的肝细胞提供足够的增殖刺激以诱导其分裂，并能够直接外推至人类。此类操作应可直接应用于患者。我们已经确定了一种肝脏部分门静脉分支栓塞方案，并证明它能诱导非人灵长类动物（猕猴）体内移植肝细胞的增殖。由于猿猴肝细胞能被源自HIV-1的慢病毒载体有效转导，该动物模型也适用于评估慢病毒介导的体外基因治疗方法。
