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stem cells:穷得要卖肾了?多养几个呗

2014-12-04 昀皓 果壳网

大自然赐予我们两个肾,但你可能为了iPhone5或iPhone6少了一个,那么,面对今后随时可能出现的新产品,小伙伴们,你们的肾还够用吗?其实,无论我们曾多少次拿“卖肾赚钱”作为笑料,但当我们真正的了解肾脏移植需求和供给比率只有可怜的几十比一、或是因肾源混乱手术偷肾案件频发等等问题时,所有人的心情都会沉重下来,并不禁会想:在生物学和医学不断发展的今天,可能在体外再造自己的肾吗?日本冈山大学的研究人

大自然赐予我们两个肾,但你可能为了iPhone5或iPhone6少了一个,那么,面对今后随时可能出现的新产品,小伙伴们,你们的肾还够用吗?

其实,无论我们曾多少次拿“卖肾赚钱”作为笑料,但当我们真正的了解肾脏移植需求和供给比率只有可怜的几十比一、或是因肾源混乱手术偷肾案件频发等等问题时,所有人的心情都会沉重下来,并不禁会想:在生物学和医学不断发展的今天,可能在体外再造自己的肾吗?

日本冈山大学的研究人员喜多村真治(Kitamura Shinji)和他的同事们发现,如果把一簇源自成年小鼠肾单位S3段的肾干细胞/祖细胞(kidney stem/progenitor cells,KS cells)悬浮培养在细胞外基质凝胶中,并相应的添加一些生长因子,那么它们就能够在体外发育成具有类似肾脏三维结构的组织。相关研究论文于今年11月25日发表在《干细胞》(stem cells)上。

肾脏是在胚胎发育时,由后肾间质(MM)和输尿管芽(UB)这两个不同的原始组织相互协调分化逐渐形成的。其中,后肾间质发育成为了肾的基本功能单位:肾单位。它由几个部分组成(如肾小球、肾小囊和肾小管等),是调节人体内水分、电解质和酸碱平衡的关键结构。同时,肾单位也会分泌某些激素。曾有人预测,因肾脏的结构非常复杂且生理功能较多,它将会成为最晚一个被成功人工体外再造的器官。

在此研究之前,已有许多科研者尝试了肾脏体外再造的研究工作。但他们大多着力于组织工程的方法,其条件复杂且难度较大。另外,也有一些研究团队尝试通过诱导多功能干细胞分化来形成肾脏。但使用这类干细胞生成器官,很可能会最终形成异位肿瘤。日本冈山大学的研究者认为,组织干细胞很可能是肾再生的理想来源,他们基于其实验室已有的相关研究结果推测,肾干细胞/祖细胞很可能是他们寻找的组织干细胞。

研究者从小鼠的肾脏中分离出所需的肾干细胞/祖细胞后,使用三维培养技术(Three‐dimensional culture)对它们进行人工的培养。同时,研究者在细胞培养基质中加入了如神经营养因子(GDNF)、碱性成纤维细胞生长因子(b‐FGF)、干细胞生长因子(HGF)、表皮生长因子(EGF)和骨形成蛋白(BMP‐7)等来帮助细胞的生长的分化。通过对不同生长因子浓度和培养细胞数量进行摸索,研究者得出了最适合的培养和诱导条件,并最终在体外培养出了一个类似肾脏三维结构的组织。

研究人员通过形态分析方法,观察研究了这些组织后确认:除了没有血管外,该组织包括了肾脏所有应该具有的生理结构,包括肾小球、近端小管、髓袢、远端小管和集合管。研究者指出,还需要进一步的实验来说明为何没有形成血管的原因。

细胞簇中所含细胞的数量与其重建肾脏结构能力之间的关系。在KS细胞培养3周后,不同结构的形成与最初培养的细胞数相关。红色:囊状的形成;蓝色:长小管的形成;绿色:端部带有球状结构的小管形成。水平轴代表KS细胞数。标尺长度:100μm。图片来源:论文原文

论文作者还指出,该研究的意义不仅局限于体外再造小鼠肾脏的可能,它也在一定程度上说明了:来自某成年个体组织的一簇干细胞/组细胞,是具有分化成该组织内各种特定细胞并进行正确定位,进而组建出该组织基本功能单位的能力的。还有一点很重要:该研究中所进行的肾发育形成过程,与需要两类组细胞(后肾间质细胞和输尿管芽细胞)协同诱导产生肾脏的胚胎肾发育过程之间,有很大的不同,这也为发育学提出了一些新的研究思路。


原始出处:

Kitamura S1, Sakurai H, Makino H.Single Adult Kidney Stem/Progenitor Cells Reconstitute 3-Dimensional Nephron Structures in Vitro.Stem Cells. 2014 Nov 25. doi: 10.1002/stem.1891. [Epub ahead of print]

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    2015-01-24 维他命
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    2015-08-01 sundong

    希望能有进展

    0

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    2015-04-11 x35042875

    AKI对心衰临床治疗意义重大,但依然需要研究检验其适用性

    0

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