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Nature:同种异体移植的iPS源心肌细胞重构灵长类心脏

2016-10-31 生物360 生物360

来自日本的研究团队利用诱导性全能干细胞源的心肌细胞同种异体移植修复了心梗猕猴的心脏功能,该研究于2016年10月10日在Nature杂志发表。诱导性全能干细胞(iPSCs)在自体移植心脏修复中具有成为受体特异性心肌细胞的潜能。然而,自体移植拥有诸多制备上和调控上的挑战。从组织相容性复合物(MHC)契合度上来说,异体移植一直都是一项颇具前景的替代手段,但是在iPSCs上付诸实践的研究却很少。在本项研


iPSCs  图片来源:counselheal.com

来自日本的研究团队利用诱导性全能干细胞源的心肌细胞同种异体移植修复了心梗猕猴的心脏功能,该研究于2016年10月10日在Nature杂志发表。

诱导性全能干细胞(iPSCs)在自体移植心脏修复中具有成为受体特异性心肌细胞的潜能。然而,自体移植拥有诸多制备上和调控上的挑战。从组织相容性复合物(MHC)契合度上来说,异体移植一直都是一项颇具前景的替代手段,但是在iPSCs上付诸实践的研究却很少。在本项研究中,研究者为我们描述了一种建立在与人类的MHC结构相似的猕猴(Macaca fascicularis)上的同种异体移植模型。纤维母细胞来源的iPSCs获得自MHC单倍(HT4)纯合子动物,随后诱导分化为心肌细胞 (iPSC-CMs)。五只HT4杂合子猴在诱导建立心梗模型后接受iPSC-CMs心肌内直接注射。移植进入体内的心肌细胞存活时间为12周,并且在服用了甲强龙和他克莫司的猴子体内未产生明显的免疫排斥。同时,利用荧光标记的钙指示分子 G-CaMP7.09,观测到移植细胞与受体自身细胞的电信号联接。在移植4周及12周之后,iPSC-CMs提高了心脏的收缩功能。尽管移植组发生室性心动过速的概率很低,但相比空白对照组来说,这一概率仍却有着显著的增加。

这一研究证实了iPSC-CMs能够在非人类的灵长类中修复心肌梗死的损伤,然而对于移植后的心率失常的控制仍需要更多的研究。

原始出处:

Yuji Shiba,et al. Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature.538, 388–391 (20 October 2016)  doi:10.1038/nature19815

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    2016-11-02 chengjn
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1687964, encodeId=4f81168e9647a, content=<a href='/topic/show?id=b3e73898423' target=_blank style='color:#2F92EE;'>#同种异体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38984, encryptionId=b3e73898423, topicName=同种异体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=23b928427427, createdName=12498768m22(暂无昵称), createdTime=Wed Aug 09 21:14:00 CST 2017, time=2017-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1881398, encodeId=da9a188139842, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 27 22:14:00 CST 2016, time=2016-11-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1677295, encodeId=51a216e729542, content=<a href='/topic/show?id=c78f66948bf' target=_blank style='color:#2F92EE;'>#灵长类#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66948, encryptionId=c78f66948bf, topicName=灵长类)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7d127484183, createdName=lg.zhao, createdTime=Wed Sep 13 20:14:00 CST 2017, time=2017-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377735, encodeId=085a13e773531, content=<a href='/topic/show?id=17b810004ce' target=_blank style='color:#2F92EE;'>#iPS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10004, encryptionId=17b810004ce, topicName=iPS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=69cb413, createdName=chengjn, createdTime=Wed Nov 02 00:14:00 CST 2016, time=2016-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1551638, encodeId=cf07155163830, content=<a href='/topic/show?id=e68d49e39c2' target=_blank style='color:#2F92EE;'>#异体移植#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49739, encryptionId=e68d49e39c2, topicName=异体移植)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bf7414204531, createdName=jianjun71, createdTime=Wed Nov 02 00:14:00 CST 2016, time=2016-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=152569, encodeId=86621525690c, content=虽然说他中化为心肌细胞,但是是不是真正的与宿主细胞整合成为一套系统,还需要研究。这个研究发现,虽然心脏的收缩功能提高了,有可能是因为干细胞的营养作用,并不是生成的新的心肌细胞,因为这些新的心肌细胞是不是有功能并不清楚, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Tue Nov 01 08:49:33 CST 2016, time=2016-11-01, status=1, ipAttribution=)]
    2016-11-01 lovetcm

    虽然说他中化为心肌细胞,但是是不是真正的与宿主细胞整合成为一套系统,还需要研究。这个研究发现,虽然心脏的收缩功能提高了,有可能是因为干细胞的营养作用,并不是生成的新的心肌细胞,因为这些新的心肌细胞是不是有功能并不清楚

    0

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