Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device.

Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device.
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DOI:
10.1038/srep21472
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发表时间:
2016-02-19
期刊:
影响因子:
4.6
通讯作者:
Ogawa T
Ogawa T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Komeya M;Kimura H;Nakamura H;Yokonishi T;Sato T;Kojima K;Hayashi K;Katagiri K;Yamanaka H;Sanjo H;Yao M;Kamimura S;Inoue K;Ogonuki N;Ogura A;Fujii T;Ogawa T

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与细胞培养不同,尤其是对于细胞系,从体内取出的组织或器官在任何培养条件下都不能长期保持。尽管微血管系统明显促进了体内局部动态平衡,但在体外模拟这样的系统是困难的,而且还没有被证明是有效的。利用小鼠精子发生的培养系统,我们解决了这一问题,并设计了一种简单的微流体装置,其中多孔膜将组织与流动的介质分开,概念上模拟了体内微血管流动与周围组织之间的关系。在该装置中培养的睾丸组织成功地维持了6个月的生精。所产生的精子具有通过微授精产生健康后代的功能。此外,该组织继续产生睾丸素,并对黄体生成素的刺激做出反应。这些数据表明,微流控装置成功地在类似活体的条件下创造了睾丸组织保持其生理功能和动态平衡的条件。因此,该装置的现有模型将为今后改善各种组织和器官的培养条件提供有价值的基础,并从整体上革命器官培养方法。
In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole.