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Hepatology:暴发性肝衰竭的新疗法

2012-09-11 庄云芳 生物通

         浙江大学医学部的研究人员在新研究中通过模型猪证实直接门静脉内移植人类骨髓间充质细胞可以阻止猪暴发性肝衰竭导致的死亡。     暴发性肝衰竭(fulminant hepatic failure,FHF)是指病前患者无肝病而突然出现大量肝细胞坏死或肝功能显着异常,并在首发症

         浙江大学医学部的研究人员在新研究中通过模型猪证实直接门静脉内移植人类骨髓间充质细胞可以阻止猪暴发性肝衰竭导致的死亡。

    暴发性肝衰竭(fulminant hepatic failure,FHF)是指病前患者无肝病而突然出现大量肝细胞坏死或肝功能显着异常,并在首发症状出现后8 周内发生肝性脑病(hepaticenc ephalopathy,HE)的一种综合征。原发病的表现有肝病面容、肝掌及皮肤血管蜘蛛痣等。肝功能衰竭的表现黄疸加深,持续低热,食欲极差、极度乏力、烦躁不安等;出现顽固性的呃逆、恶心、呕吐及明显的腹胀;有明显的出血倾向。其临床特点是起病急、进展快、病情危重。虽然目前各种治疗措施较多,使FHF患者的预后很大改善,但其病死率仍在50%以上。

    近年来动物实验和一些非随机性临床试验证实了人类骨髓间充质细胞(hBMSC)移植治疗急性和慢性肝损伤的效力。然而,当前没有没有研究探讨hBMSC移植在FHF治疗,尤其是在大型动物模型中的作用。

    新研究旨在证实在猪中通过门静脉途径移植hBMSC治疗FHF的安全性、效力和潜在机制。研究人员在给予猪D-半乳糖胺(D-galactosamine)注射后直接将人类BMSCs经门静脉途径或外周静脉注入了FHF猪体内,对照组则接受了无细胞的门静脉移植。外周静脉移植和对照组的所有动物在96小时内均死于FHF。

    相比之下,门静脉移植组的15只动物中有13只获得了长期生存,时间超过6个月。免疫组织化学证实在存活动物中移植的hBMSC衍生的干细胞从第2周-第10周广泛分布在肝小叶和肝实质中。30%的干细胞是由hBMSC衍生。然而,在第15周移植细胞的数量显着下降。到第20周时只有少量的单细胞分散在再生肝小叶中,肝组织显示接近正常结构。

    研究结果表明直接门静脉移植hBMSCs是一条安全有效治疗FHF的途径。这些移植的hBMSCs有可能在FHF的初期阶段通过增殖和转分化为干细胞快速参与了肝再生。这种方法有可能在未来被用于临床研究。



 

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    2012-09-13 gwc384
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    2012-09-13 kcb074
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