动物模型及少量非随机临床试验证明移植人骨髓间充质干细胞（hBMSC）具有治疗急性及慢性肝损伤的功效。然而尚无关于hBMSC治疗暴发性肝衰竭（FHF）的研究，尤其是使用大型动物（猪）模型的研究。本研究的目的是，探讨移植hBMSC到肝门静脉系统中用于治疗猪暴发性肝衰竭的安全性、疗效及相关的潜在机制。注射D-氨基半乳糖诱导猪FHF后，立即经由门静脉或外周静脉移植hBMSC（细胞数：3×107），同时设置经门静脉移植（IPT）但没有细胞的假手术组作为对照（设置IPT组、经外周静脉移植（PVT）组及对照组，每组包含15只猪）。PVT及对照组的所有动物在96小时内死亡。相反的，IPT组中13/15的动物能够长时间的存活（﹥6个月）。免疫组织化学证明，在移植后2～10周内，由hBMSC分化为的肝细胞广泛分布于存活动物的肝小叶及肝实质中。30%的肝细胞是由hBMSC分化而来。然而在第15周时移植的细胞数显著下降。在第20周时只有少量单个移植细胞分布于肝小叶中，同时肝组织结构显示几乎正常。结论：直接经由肝门静脉内移植hBMSC治疗FHF是安全有效的。移植的hBMSC在FHF的初始阶段可通过快速增值分化为肝细胞参与肝再生。此方法可能在将来用于临床治疗。
第三军医大学西南医院感染科 朱鹏 王宇明 摘译
本文首次发表于[Journal of Hepatology ,2012;56:1044-1052]
本文首次发表于[Journal of Hepatology ,2012;56:1044-1052]
Immediate Intraportal Transplantation of Human Bone Marrow Mesenchymal Stem Cells Prevents Death From Fulminant Hepatic Failure in Pigs
The effectiveness of human bone marrow mesenchymal stem cell (hBMSC) transplantation to treat acute and chronic liver injury has been demonstrated in animal models and in a few nonrandomized clinical trials. However, no studies have investigated hBMSC transplantation in the treatment of fulminant hepatic failure (FHF), especially in large animal (pig) models. The aim of this study was to demonstrate the safety, effectiveness, and under-lying mechanism of hBMSC transplantation for treating FHF in pigs through the intra-portal route. Human BMSCs (3 107) were transplanted into pigs with FHF via the intraportal route or peripheral vein immediately after D-galactosamine injection, and a sham group underwent intraportal transplantation (IPT) without cells (IPT, peripheral vein transplantation [PVT], and control groups, respectively, n = 15 per group). All of the animals in the PVT and control groups died of FHF within 96 hours. In contrast, 13 of 15 animals in the IPT group achieved long-term survival (>6 months). Immunohistochemistry demonstrated that transplanted hBMSC-derived hepatocytes in surviving animals were widely distributed in the hepatic lobules and the liver parenchyma from weeks 2 to 10. Thirty percent of the hepatocytes were hBMSC-derived. However, the number of transplanted cells decreased significantly at week 15. Only a few single cells were scattered in the regenerated liver lobules at week 20, and the liver tissues exhibited a nearly normal structure. Conclusion: Immediate IPT of hBMSCs is a safe and effective treatment for FHF. The transplanted hBMSCs may quickly participate in liver regeneration via proliferation and transdifferentiation into hepatocytes during the initial stage of FHF. This method can possibly be used in future clinical therapy. (H EPATOLOGY 2012;56:1044-1052)
（浙江大学李兰娟院士领衔完成的一项最新研究）
