Diabetologia:鉴定促进人iPSCs / ESC和小鼠胚胎胰腺移植到胰腺内分泌细胞的小分子

2017-08-06 MedSci MedSci原创

由人诱导的多能干细胞(hiPSC)或人类胚胎干细胞(hESCs)产生的胰腺β样细胞提供了非常有前景的供体组织来源。然而,由于使用生长因子的分化方案非常昂贵。因此,在这项研究中,研究人在建立有效的分化方案,试图使用新的小分子诱导剂将hiPSCs / hESC转变为胰岛素(INS)+细胞。

近日,国际杂志 《Diabetologia》上在线发表一项关于鉴定促进人iPSCs / ESC和小鼠胚胎胰腺移植到胰腺内分泌细胞的小分子的研究。

由人诱导的多能干细胞hiPSC)或人类胚胎干细胞hESCs)产生的胰腺β样细胞提供了非常有前景的供体组织来源。然而,由于使用生长因子的分化方案非常昂贵。因此,在这项研究中,研究人在建立有效的分化方案,试图使用新的小分子诱导剂将hiPSCs / hESC转变为胰岛素(INS+细胞。

研究人员筛选了来自于hESC衍生的胰腺和十二指肠同源异型盒1PDX1+胰腺祖细胞的小分子,它能增加INS+细胞诱导率。利用hit化合物对从hiPSCs / hESCs中生成INS+细胞的分化流程进行了优化,且用化合物诱导的INS +细胞具有自身体外和体内功能。此外,在外植体培养系统中使用小鼠胚胎胰腺组织检查该化合物的诱导活性。最后,对INS+细胞进行RNA测序分析,以阐明该化合物诱导胰腺内分泌分化的作用机制。

在大约1250个筛选的小分子中鉴定出一种化合物,即色甘酸钠(SCG)。当SCG与先前描述的方案组合时,INS +细胞的诱导率从5.9±1.5%(n=3)的平均值±SD 增加到16.5±2.1%(n=3)。SCG诱导的神经细胞因子3阳性细胞的平均值±SD32.6±4.6%(n =3), 而无SCG的对照治疗组为14.2±3.6%(n = 3),导致内分泌细胞产生增加,包括胰岛素生产细胞。类似的被SCG诱导确认使用老鼠胚胎胰腺外植体。SCG的诱导胰腺内分泌分化包括抑制骨形成蛋白4的信号的机制也被证实。

研究发现,SCG通过促进内分泌前体的分化改善多个来自hiPSC/hESC系和小鼠胚胎胰腺外植体胰腺内分泌细胞的产生。这一发现将有助于阐明胰腺内分泌发育的机制,并促进从hiPSCs/hESCs成功地产生INS +细胞。

原始出处:

Yasushi Kondo, Taro Toyoda, Ryo Ito,et al. Identification of a small molecule that facilitates the differentiation of human iPSCs/ESCs and mouse embryonic pancreatic explants into pancreatic endocrine cells

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    2018-04-21 gwc392
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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-09-16 宋威
  5. 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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-08-10 虈亣靌

    体外与体内还有很长时间的路要走,希望顺利吧

    0

  6. 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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-08-08 ailian1202
  7. 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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-08-08 chengjn
  8. 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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-08-08 gjsgj
  9. 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createdBy=ffb85431490, createdName=caoliehu, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538817, encodeId=0d4e153881e2b, content=<a href='/topic/show?id=60de100065b' target=_blank style='color:#2F92EE;'>#iPSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10006, encryptionId=60de100065b, topicName=iPSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37d013060412, createdName=neurosurgeon, createdTime=Tue Aug 08 02:38:00 CST 2017, time=2017-08-08, status=1, ipAttribution=)]
    2017-08-08 caoliehu
  10. 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    2017-08-08 neurosurgeon

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昨天,两篇有关干细胞临床试验治疗黄斑变性的文章同时发表在权威期刊《新英格兰医学杂志》上,但是他们的结果却截然不同!

STM:基因改造过的诱导性多功能干细胞(iPSCs)可治疗隐性遗传营养不良型大疱性表皮松解症(RDEB)

隐性遗传营养不良型大疱性表皮松解症(RDEB) 是一种遗传疾病。它是由于VII型胶原的编码基因变异导致的。RDEB患者的皮肤很脆弱并且很容易在接收到压力时起水疱。特别是对于RDEB这种在现阶段没有有效治疗的疾病,使用诱导性多功能干细胞(iPSCs)有从根本上改变疾病细胞治疗的潜力。为了证明诱导性多功能干细胞(iPSCs)可以治疗RDEB,研究者们从有VII型胶原基因(Co17a1)变异的小鼠中提取

N Engl J Med:自体诱导干细胞产生的视网膜细胞用于治疗黄斑变性

研究人员评估了在新生血管性年龄相关性黄斑变性患者中,移植从诱导多能干细胞(iPSCs)中分离的视网膜色素上皮细胞(RPE)片的可行性。iPSC从两名晚期新生血管性年龄相关性黄斑变性患者的皮肤成纤维细胞产生,并分化为RPE细胞。RPE细胞和共同来源的iPSC经过严格的测试。在其中一位患者中进行包括去除新生血管膜,并在视网膜下移植自体iPSC衍生的RPE细胞片的手术。手术后1年,移植片保持完整,矫正视

Nature:重编程细胞同源移植也会发生排斥反应

6月9日出版的自然杂志继5月刊发加州大学圣地亚哥分校的研究人员有关诱导多能干细胞(iPSCs)论文,再次刊登有关该研究的一篇快报,并予以评论,称研究人员在小鼠中证实将诱导多能干细胞(iPSCs)分化生成的多种组织移植至动物体内会产生快速的免疫排斥反应,即便iPSCs的起源细胞来自于移植小鼠本身。一直以来,大多数科学家们都认为来自于个人自身组织的重编程细胞能够被安全地移植到同一个体体内并能避免排斥反