Nature:人造胰岛有望攻克糖尿病 

2020-08-20 MedSci原创 MedSci原创

缺乏PD-L1的人造胰岛类器官的功能会逐渐丧失,导致机体血糖水平的增加,而PD-L1+的人造胰岛类器官则可以维持血糖稳态超过50天。

胰岛移植为1型和2型糖尿病晚期患者提供了良好的长期血糖控制。然而,尸体胰岛的可用性和质量限制了该疗法的成功和实用性。诱导多能干细胞(iPS细胞)分化为产生胰岛素的β样细胞是一项重大进展,从干细胞衍生的人造胰岛为治疗胰岛素依赖性糖尿病带来了希望,但这一目标的实现仍然存在很多的挑战。

最近,研究人员在Nature杂志发文,报导从诱导的多能干细胞生成人类胰岛样类器官(HILOs)的方法,并发现非经典的WNT4信号可以驱动其代谢成熟,是体外葡萄糖刺激后大量胰岛素分泌所必需的。

这些功能成熟的HILOs中含有类似内分泌的细胞类型,移植后可迅速重建糖尿病NOD/SCID小鼠的葡萄糖稳态。

移植胰岛的临床效用受到异源性和自身免疫反应的限制。值得注意的是,健康胰岛中的细胞子集包括了少量的β细胞,其被发现表达PD-L1,PD-L1是β细胞免疫耐受性的已知决定因素。因此,研究人员做出假设,外源性PD-L1表达可以保护人造胰岛类器官在移植时免受免疫排斥。

表达PD-L1的人造胰岛类器官在人源化小鼠中提供更长时间的葡萄糖控制

 

为了研究这个概念,研究人员使用慢病毒系统生成表达PD-L1的hiPS细胞克隆,随后分化成代谢成熟的人造胰岛类器官。PD-L1过表达不影响胰岛素的表达。将具有和不具有PD-L1表达的人造胰岛类器官移植到免疫功能正常的糖尿病小鼠中,在移植后数天内可以恢复血糖控制,且两者疗效相似。然而,研究人员发现,缺乏PD-L1的人造胰岛类器官的功能会逐渐丧失,导致机体血糖水平的增加,而PD-L1+的人造胰岛类器官则可以维持血糖稳态超过50天。

此外,体外用干扰素-γ刺激可以诱导内源性PD-L1的表达,限制T细胞活化和移植排斥。

因此,该研究报导了能够逃避免疫检测的具有葡萄糖反应性的胰岛类器官的生成,为治疗糖尿病提供了一种有希望的新疗法。

 

原始出处:

Eiji Yoshihara et al. Immune-evasive human islet-like organoids ameliorate diabetes, Nature (2020). 

 

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    2021-01-04 liye789132251
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    2021-07-05 baoya
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    2020-12-08 148ccaa6m02暂无昵称

    我觉得还是去氢骆驼蓬碱来的靠谱

    0

  4. 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createdBy=48aa31545372, createdName=zjshifan_98647316, createdTime=Sun Aug 30 07:16:19 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891927, encodeId=fd6d89192ea5, content=希望,总是希望但为啥就没有结果呢!最后又是失望, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10535425256, createdName=ms2000000624889280, createdTime=Wed Oct 14 08:16:19 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=814266, encodeId=449881426623, content=学习下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b855412177, createdName=ms5000000674364761, createdTime=Thu Aug 27 18:57:23 CST 2020, time=2020-08-27, status=1, 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20:28:58 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
  5. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813761, encodeId=d222813e6172, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:08:59 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811620, encodeId=73a881162020, content=牛逼!, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:25:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811595, encodeId=69cd811595a7, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKM5opSMdO81JdZ2M7o9npdRIaB2cqAxzEC1Q9Hqht0VPJlxnQMx1IhAYibaFXYKg7emtfR6hkpZtA/132, createdBy=96432493356, createdName=yhthzx, createdTime=Thu Aug 20 22:46:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811571, encodeId=9ac38115e1cd, content=新希望<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 20:28:58 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-10-14 ms2000000624889280

    希望,总是希望但为啥就没有结果呢!最后又是失望

    0

  6. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813761, encodeId=d222813e6172, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:08:59 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811620, encodeId=73a881162020, content=牛逼!, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:25:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811595, encodeId=69cd811595a7, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKM5opSMdO81JdZ2M7o9npdRIaB2cqAxzEC1Q9Hqht0VPJlxnQMx1IhAYibaFXYKg7emtfR6hkpZtA/132, createdBy=96432493356, createdName=yhthzx, createdTime=Thu Aug 20 22:46:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811571, encodeId=9ac38115e1cd, content=新希望<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 20:28:58 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-27 ms5000000674364761

    学习下

    0

  7. 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createdBy=48aa31545372, createdName=zjshifan_98647316, createdTime=Sun Aug 30 07:16:19 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891927, encodeId=fd6d89192ea5, content=希望,总是希望但为啥就没有结果呢!最后又是失望, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10535425256, createdName=ms2000000624889280, createdTime=Wed Oct 14 08:16:19 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=814266, encodeId=449881426623, content=学习下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b855412177, createdName=ms5000000674364761, createdTime=Thu Aug 27 18:57:23 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=813761, encodeId=d222813e6172, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64245268311, createdName=14818eb4m67暂无昵称, createdTime=Thu Aug 27 08:08:59 CST 2020, time=2020-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811620, encodeId=73a881162020, content=牛逼!, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Thu Aug 20 23:25:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811595, encodeId=69cd811595a7, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKM5opSMdO81JdZ2M7o9npdRIaB2cqAxzEC1Q9Hqht0VPJlxnQMx1IhAYibaFXYKg7emtfR6hkpZtA/132, createdBy=96432493356, createdName=yhthzx, createdTime=Thu Aug 20 22:46:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811571, encodeId=9ac38115e1cd, content=新希望<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 20:28:58 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-27 14818eb4m67暂无昵称

    学习了

    0

  8. 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level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKM5opSMdO81JdZ2M7o9npdRIaB2cqAxzEC1Q9Hqht0VPJlxnQMx1IhAYibaFXYKg7emtfR6hkpZtA/132, createdBy=96432493356, createdName=yhthzx, createdTime=Thu Aug 20 22:46:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811571, encodeId=9ac38115e1cd, content=新希望<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 20:28:58 CST 2020, time=2020-08-20, status=1, ipAttribution=)]
    2020-08-20 ms3000000449926787

    牛逼!

    0

  9. 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level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKM5opSMdO81JdZ2M7o9npdRIaB2cqAxzEC1Q9Hqht0VPJlxnQMx1IhAYibaFXYKg7emtfR6hkpZtA/132, createdBy=96432493356, createdName=yhthzx, createdTime=Thu Aug 20 22:46:09 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=811571, encodeId=9ac38115e1cd, content=新希望<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200529/3611e9bb629c4e5b81fbd8ce784b06cc/128487eae357460bb98f67d86230c218.jpg, createdBy=ab235268530, createdName=神盾医疗局局长Jack, createdTime=Thu Aug 20 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    2020-08-20 yhthzx

    厉害了👍

    0

  10. 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