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Nature：新开发人工水凝胶能实现体外器官培养批量化生产

2016-11-18 生物探索 生物探索

人工水凝胶体外器官培养批量化生产
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类器官是可以从一个人的干细胞开始从实验室培育的小型器官，它们可以用于疾病的模型，在未来用来测试药物，甚至取代患者的受损组织。但是目前的类器官在标准化生长和可控制的方式上还是非常困难，这是设计和应用它们的关键。瑞士洛桑联邦理工学院（EPFL）的科学家通过开发一个正在申请专利的“水凝胶”解决了这个问题，为类器官的生长提供了完全可控、可调的方式。这个突破11月16日在线发表在Nature上。1 类器官需

类器官是可以从一个人的干细胞开始从实验室培育的小型器官，它们可以用于疾病的模型，在未来用来测试药物，甚至取代患者的受损组织。但是目前的类器官在标准化生长和可控制的方式上还是非常困难，这是设计和应用它们的关键。瑞士洛桑联邦理工学院（EPFL）的科学家通过开发一个正在申请专利的“水凝胶”解决了这个问题，为类器官的生长提供了完全可控、可调的方式。这个突破11月16日在线发表在Nature上。




1 类器官需要一个三维的支架

用干细胞培养类器官的话，干细胞需要在包含促进干细胞的更新和分化的混合生物分子的三维凝胶中生长。这些凝胶的作用是模仿干细胞的自然环境，为它们提供了一种富含蛋白质和糖的支架，称为“细胞外基质”，在此基础上干细胞建立特定的身体组织。干细胞粘到细胞外基质凝胶上后，“自组织”成如视网膜，肾，或肠的微型器官。这些微小的器官保留了他们真实生物学中的关键方面，可以用于研究疾病或在人体试验之前测试药物。



目前作为类器官生长的凝胶来自小鼠，存在一些问题：首先不可能批量生产，这使干细胞的行为不一致。其次，生化的复杂性要让它们调整一致来研究不同参数（例如生物分子、机械性能等）对细胞生长的影响非常困难。最后，该凝胶可能携带病原体或抗原，这意味着它们不适合培养用于临床的类器官。

2 人工水凝胶溶液解决问题

在EPFL生物工程研究所的Matthias Lütolf实验室已经开发出了一种合成的水凝胶，避开了自然衍生的凝胶的传统局限性。正在申请专利的凝胶是由水和聚乙二醇——在今天以各种形式，从面霜到牙膏工业都广泛应用的一种物质，在这种情况下用于生物工程。

该研究的第一作者Nikolce Gjorevski和他的同事用人工水凝胶将肠道干细胞培养成微型的肠。功能性水凝胶不仅是一个目标和本身，也是一种识别影响干细胞扩增和形成类器官能力的因素的手段。通过仔细调整水凝胶的特性，他们发现类器官形成过程的不同阶段需要不同的力学环境和生物成分。

其中这样一个因子叫做纤连蛋白，它有助于干细胞附着在水凝胶上。Lütolf的实验室发现这种附着对于类器官的生长是非常重要的。因为它引发了干细胞的整个一系列的信号，告诉它们生长和建立肠状的结构。研究人员还发现了机械性能的重要作用，比如凝胶的物理刚度在调节肠干细胞行为上的作用，揭示了细胞如何能够感受、经历和对物理刺激做出反应。这种了解是非常有价值的，干细胞的生化信号的影响很好理解，物理因素的影响更加神秘。

由于这种水凝胶是人工制造的，所以很容易控制其化学成分和关键性能，并确保每一批次的一致性。因为它是人工的，所以它不携带任何感染或触发免疫反应的风险。因此，它提供了将类器官从基础研究推广到未来的药物筛选和临床应用的手段。




Lütolf的实验室正在研究其他类型的干细胞，以拓展水凝胶应用到其它组织的能力。

原始出处：

Nikolce Gjorevski,et al. Designer matrices for intestinal stem cell and organoid culture. Nature.16 November 2016.

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    2017-02-06 liye789132251

    #Nat#

    0

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    2016-11-20 tastas

    #水凝胶#

    0

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    2016-11-20 lishizhe

    #凝胶#

    0

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    2016-11-20 ms1343860338762272

    #生产#

    0

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    2016-11-18 457432304

    希望这一技术能够早日成熟

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1881448, encodeId=1496188144895, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Feb 06 07:51:00 CST 2017, time=2017-02-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307991, encodeId=8145130e99191, content=<a href='/topic/show?id=edd364149bc' target=_blank style='color:#2F92EE;'>#水凝胶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64149, encryptionId=edd364149bc, topicName=水凝胶)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=47c5349, createdName=tastas, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460920, encodeId=a1c6146092032, content=<a href='/topic/show?id=de4331310a4' target=_blank style='color:#2F92EE;'>#凝胶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31310, encryptionId=de4331310a4, topicName=凝胶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e09e6383467, createdName=lishizhe, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517714, encodeId=d564151e71482, content=<a href='/topic/show?id=44156886664' target=_blank style='color:#2F92EE;'>#生产#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68866, encryptionId=44156886664, topicName=生产)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37a111112788, createdName=ms1343860338762272, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156618, encodeId=d1391566180b, content=希望这一技术能够早日成熟, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/6A46DA8C6FB1943F023CA19C951ABE5D/100, createdBy=81aa1978024, createdName=457432304, createdTime=Fri Nov 18 14:12:36 CST 2016, time=2016-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156604, encodeId=783a156604fe, content=人类的智慧, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161224/IMG585DA5E26B9F44696.jpg, createdBy=565a98798, createdName=susice, createdTime=Fri Nov 18 12:55:53 CST 2016, time=2016-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156600, encodeId=fd4d15660035, content=科学真的好强大, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKDtuWHtWxToIW0ZEvbHgDb4ibqQ1xaDQxcsHC5NIc2RJUxQgHJOLGEg8OUT345rDPmka4icU0WHPgw/0, createdBy=379f1941464, createdName=艳阳天2016, createdTime=Fri Nov 18 12:49:43 CST 2016, time=2016-11-18, status=1, ipAttribution=)]
    2016-11-18 susice

    人类的智慧

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1881448, encodeId=1496188144895, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Feb 06 07:51:00 CST 2017, time=2017-02-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307991, encodeId=8145130e99191, content=<a href='/topic/show?id=edd364149bc' target=_blank style='color:#2F92EE;'>#水凝胶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64149, encryptionId=edd364149bc, topicName=水凝胶)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=47c5349, createdName=tastas, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1460920, encodeId=a1c6146092032, content=<a href='/topic/show?id=de4331310a4' target=_blank style='color:#2F92EE;'>#凝胶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31310, encryptionId=de4331310a4, topicName=凝胶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e09e6383467, createdName=lishizhe, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517714, encodeId=d564151e71482, content=<a href='/topic/show?id=44156886664' target=_blank style='color:#2F92EE;'>#生产#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68866, encryptionId=44156886664, topicName=生产)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37a111112788, createdName=ms1343860338762272, createdTime=Sun Nov 20 02:51:00 CST 2016, time=2016-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156618, encodeId=d1391566180b, content=希望这一技术能够早日成熟, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/6A46DA8C6FB1943F023CA19C951ABE5D/100, createdBy=81aa1978024, createdName=457432304, createdTime=Fri Nov 18 14:12:36 CST 2016, time=2016-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156604, encodeId=783a156604fe, content=人类的智慧, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161224/IMG585DA5E26B9F44696.jpg, createdBy=565a98798, createdName=susice, createdTime=Fri Nov 18 12:55:53 CST 2016, time=2016-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=156600, encodeId=fd4d15660035, content=科学真的好强大, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKDtuWHtWxToIW0ZEvbHgDb4ibqQ1xaDQxcsHC5NIc2RJUxQgHJOLGEg8OUT345rDPmka4icU0WHPgw/0, createdBy=379f1941464, createdName=艳阳天2016, createdTime=Fri Nov 18 12:49:43 CST 2016, time=2016-11-18, status=1, ipAttribution=)]
    2016-11-18 艳阳天2016

    科学真的好强大

    0