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Cell:肝脏再生能力为何如此强大?终于找到原因了!

2015-08-14 MedSci MedSci原创

在人体的所有器官中,肝脏的再生能力最为强大。至于肝脏如何进行自我修复及再生,专家学者们尚未得到统一的结果。一项新进研究揭示了一种不明细胞对肝脏再生具有重要意义,它可以使肝脏组织得以再生却不会形成肿瘤。这些新发现的细胞也称为肝细胞,但是它的功能比普通的肝细胞更强大。在既往研究中,研究人员认为肝脏中的一类成体干细胞即卵圆细胞在肝脏的再生功能中发挥着重要作用,但是后续研究证实卵圆细胞最后分化为胆管细胞。

在人体的所有器官中,肝脏的再生能力最为强大。至于肝脏如何进行自我修复及再生,专家学者们尚未得到统一的结果。一项新进研究揭示了一种不明细胞对肝脏再生具有重要意义,它可以使肝脏组织得以再生却不会形成肿瘤。这些新发现的细胞也称为肝细胞,但是它的功能比普通的肝细胞更强大。在既往研究中,研究人员认为肝脏中的一类成体干细胞即卵圆细胞在肝脏的再生功能中发挥着重要作用,但是后续研究证实卵圆细胞最后分化为胆管细胞。 




加利福尼亚大学圣地亚哥分校医学院的研究人员发现,“混合肝细胞”是肝脏具有强大再生功能的根本原因。他们将研究结果发表在Cell。

药理学和病理学教授Michael Karin说道:“利用杂种肝细胞是治疗肝脏病变最有效的方案,而且通过干细胞移植是避免出现肝衰竭最安全的方式。”

如果患者患有一些影响肝脏再生能力的疾病如肝硬化和肝炎,在今后完全可以采用细胞移植的方式治疗,并恢复肝脏功能。如果患者患有肝硬化,则会导致一系列并发症的出现,如食管胃底静脉曲张。在美国,导致肝硬化最常见的病因是酗酒和肝炎。

将小鼠暴露于四氯化碳这种有毒环境下之后,研究人员密切关注着肝脏的修复过程。在肝脏的自我修复过程中,他们在肝门处发现了混合肝细胞。在肝脏出现慢性损伤之后,这些肝细胞广泛进行增殖,对肝脏进行修复。由于这些细胞与正常的肝细胞相似,但表达出的基因为低水平的胆管细胞特异性基因,研究人员将它们称为是“混合肝细胞(Hybrid hepatocytes,HybHP )”。

“虽然混合肝细胞并非干细胞,但是截至到目前为止,利用混合肝细胞治疗肝衰竭患者最为有效。” Joan Font-Burgada教授如是说道。

目前,许多研究人员正在检测诱导多能干细胞(iPSCs)修复受损肝脏的能力,以避免患者出现肝衰竭并发症。使用诱导多能干细胞是非常困难的,但是,一旦可以使用iPSCs对患者的受损肝脏进行治疗,则肝细胞再生的速度和能力令人惊叹。但是必须承认的是,患者患肿瘤的风险也相应增加。

研究人员对三组肝癌小鼠(各组小鼠患肝癌的类型不同)进行了评估和相应检查,他们发现,并没有证据证明混合肝细胞可以导致肝癌的出现和恶化。因此研究人员认为,混合肝细胞并不会引起肝病患者出现肝癌。

尽管大多数的研究以小鼠为实验对象进行,研究人员希望在人体中也可以找到人类的肝脏混合肝细胞,且人的混合肝细胞与小鼠的混合肝细胞的功能相似,都可以促使肝脏组织的再生和自我修复。我们相信,会有那么一天,对于肝衰竭的患者,不需肝移植,只需细胞移植便可拯救患者生命。

原始出处:
Michael Karin et al., Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer, Cell, doi: 10.1016/j.cell.2015.07.026, published 13 August 2015, abstract.

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    2016-05-14 智智灵药
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    2015-08-18 wodexinxi

    “杂交肝细胞”

    0

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    2015-08-16 acount

    很好的!!!

    0

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    2015-08-16 shenyifeiyang

    讲的好!

    0

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