Dev Cell:细胞张力能使心脏细胞更强壮

2017-10-16 佚名 "细胞“微信号

即使在医疗科技十分发达的现在,当人类心脏病发作之后,并不能完全治愈,而斑马鱼的心脏细胞却可以轻而易举取代原本丢失或被疾病侵害的细胞。因此科学家花了很长的时间探究这条小鱼的再生能力,期望找到可以改善现有治疗人类心脏疾病的方式。

即使在医疗科技十分发达的现在,当人类心脏病发作之后,并不能完全治愈,而斑马鱼的心脏细胞却可以轻而易举取代原本丢失或被疾病侵害的细胞。因此科学家花了很长的时间探究这条小鱼的再生能力,期望找到可以改善现有治疗人类心脏疾病的方式。

一项发布在 9 月 25 日发行的《发育细胞》(Developmental Cell)期刊的 研究成果,发现了细胞张力对心脏细胞再生的影响。作用在细胞上的力学张力,决定了这种波前性质及随后造成的组织细胞再生。实验结果展现了新的典范,显示在组织中作用的力可直接指导丢失组织进行细胞再生的走向。

研究人员借由拍摄斑马鱼心脏微小跳动的影片,发现能在培养皿中使细胞再度生长,影片也捕获到这些细胞令人意想不到的行为。研究人员发现原以为消耗殆尽的心脏组织竟然能在波浪中再生!它们是由移动快速的超大型领导细胞在前方引领,并被体型较小的细胞拖延以产生其他细胞。

杜克大学(Duke University)医学院细胞生物学所 Ken Poss 教授实验室的博士后研究员兼本研究首席研究员 Jingli Cao 博士说:“我们的研究成果为再生组织的细胞周期动力学奠定了基础。透过操作细胞的力学张力,我们可能也可以开发新的生物工程技术或转译方法。”

2015 年,Cao 博士和同事已能做到将斑马鱼的心脏移除后放入培养皿,观察它的生长。在这项研究中,他们监测心外膜的再生情况,这是一层包覆在心脏表面的薄膜。令人惊讶的是他们发现心房和心室依然继续跳动,彷佛这颗心脏仍长在斑马鱼体内。

研究人员摧毁了大部分心外膜,再将外植体器官置于显微镜下,希望能捕捉到动态的再生情形。他们原本预期看到一群细胞迅速复制 DNA 并分裂为新细胞,随后补充器官表面丢失的细胞,然而事实并非如此。当然以上情况绝对会发生,但这并不是最主要的方法。相反地,再生过程是由已复制 DNA 却不分裂的细胞主导,因此能有效制造出超大型细胞。

Cao 博士说:“想像一下你皮肤有个伤口,你想尽快覆盖它,但你却没有足够的细胞。借由细胞变大,你就可以有效地覆盖伤口。我们认为这种策略能以更高效率的方式提高覆盖面积,同时增加再生能力。”Poss 教授则表示:“这项研究试着了解当细胞再生时,会如何做决策。如果有方法影响细胞做决策,引导细胞再生,形成更大的细胞,或在分裂时产生更多细胞,那么这可能是影响组织修复能力的重要关键。”

研究人员测量了在再生波前的细胞特性,发现与较小的跟随细胞相比,较大的再生细胞会以较快的速度穿越心脏表面。当测量细胞膜张力时,他们发现施加微小的切口后,领导细胞的回弹速度比跟随细胞快,就像灌饱气的气球爆裂后缩回原样。可以说是这样的力学张力让细胞维持在复制完 DNA 后不会分裂。

研究人员计划使用斑马鱼心脏外植体培养系统,筛选可能增加心脏组织再生能力的小分子。这些化学物质可能成为未来研发用以修复心脏疾病或其他心血管疾病新药的基础。看似平凡且每个细胞都有的细胞张力,竟能大大影响细胞再生能力,甚至有机会使人类心脏细胞再生成为可能,实在很不可思议啊!

原始出处:

Cao, J., et al., Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue. Dev Cell, 2017. 42(6): p. 600-615 e4.

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    2018-05-27 fzwish20000
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    2018-07-05 维他命
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    2017-12-15 zhmscau
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    2017-10-22 lou.minghong

    新知识.学习了.

    0