去年Nature今年Cell:无需精子、卵子或子宫,以色列科学家培育出人工合成胚胎

2022-08-09 nagashi “生物世界”公众号

首次在子宫外培育出完全人工合成的小鼠胚胎。这些胚胎并不是精子和卵子的产物,而是完全由培养在培养皿中的干细胞发育而来,并且它们在一个体外构建的“人造子宫”中生长。

你是否想象过这样一个场景:未来的人类在一个容器里孕育生长,而且无需精子和卵子的结合,只需一小团细胞便能制造出许多“新人类”。人造子宫,无性繁殖,这些概念似乎只存在于科幻作品中,但随着科学技术的发展,这些科幻概念正在一步步写入现实。

2022年8月1日,以色列魏茨曼科学研究所的 Jacob H. Hanna 团队在 Cell 期刊发表了题为:Post-Gastrulation Synthetic Embryos Generated Ex Utero from Mouse Na?ve ESCs 的研究论文[1]

该研究首次在子宫外培育出完全人工合成的小鼠胚胎。这些胚胎并不是精子和卵子的产物,而是完全由培养在培养皿中的干细胞发育而来,并且它们在一个体外构建的“人造子宫”中生长。

“合成胚胎”和“人造子宫”

如今,在各种因素的主导下,许多国家的生育率都在下降,2020年《柳叶刀》上发表的一项研究预测,世界人口可能会在2064年达到约97亿人的峰值,然后在2100年下降到约88亿人[2]

在快节奏的现代社会,孕育一个胎儿的时间成本和物质成本急剧增加,再加上分娩时的巨大疼痛和潜在的风险,种种问题导致现在越来越多的年轻人不再那么愿意生育,而人造子宫正是在这种背景下应运而生。

早在2021年3月,Jacob H. Hanna 团队就在 Nature 期刊在线发表了题为:Ex utero mouse embryogenesis from pre gastrulation to late organogenesis 的研究论文[3]。该研究创建了一个人造机器子宫,并在在体外条件下维持天然小鼠胚胎存活11天,且胚胎在人造子宫培育过程中发育正常。详情:以色列科学家首次在人造子宫中培养哺乳动物胚胎

他们开发的这个人造子宫系统,小鼠胚胎能在其中正常生长6天时间,这是小鼠20天完整妊娠期的大约三分之一,此时,培养的小鼠胚胎已经可以明显看出身体结构和器官了。

如今,在这项最新研究中,研究团队做出了更大胆的尝试,即无需天然胚胎,而是通过干细胞制成人工胚胎,直接在人造子宫中进行培养。

研究小组将“人造子宫”系统与一种新型的干细胞混合物相结合,这种干细胞混合物中的部分细胞已经化学诱导处理,一些在胎盘和卵黄囊发育阶段的关键基因(如Cdx2和GATA-4)被过表达,而上述两种组织对于胚胎的健康生长至关重要。

人工诱导产生“合成胚胎”,并在“人造子宫”中培养

这些“合成胚胎”可以在“人造子宫”中生长到第8.5天(小鼠的整个妊娠期约为20天),并成功发育出形态良好的大脑、神经管、肠道以及正常跳动的心脏等组织。更重要的是,通过分析合成胚胎在不同组织中的基因表达模式,研究人员发现它们与天然状态下胚胎的相似度高达95%。

合成胚胎和天然胚胎的基因表达模式的相似度高达95%

该研究的通讯作者 Jacob Hanna 教授感叹道:我们发现这些细胞有着难以置信的自我组织能力,在给予合适的人工设备支持时,就可以释放这种能力。

Jacob Hanna 教授

值得注意的是,虽然这项研究成果的进步性令人惊叹,但它也存在一些局限性。例如:第8.5天仅仅是胚胎发育的早期阶段,距离整个妊娠期结束还太早;每10000个细胞团中,大约只有50个自组织成胚胎,其余部分均发育不良。

推动发育生物学的发展

尽管如此,这项研究工作也为发育生物学的基础研究打开了新的大门。如今,科学家们可以很容易地将成熟体细胞恢复到更原始的干细胞状态,但要弄清楚哪些化学信号会诱导干细胞产生肝脏或肾脏的前体,则是一项更具挑战性的工作。

Jacob Hanna 教授团队的这项新研究无疑为正确使用这些配方致提供一条前进的道路:透明的“人造子宫”可以允许发育生物学家实时观察器官的发育情况;并且因为从干细胞开始,而不是受精卵,它们可以以一种更具伸缩性和可控性的方式产生这些胚胎结构。

透明的“人造子宫”允许发育生物学家实时观察器官的发育情况

对于这项研究,维也纳科学院分子生物技术研究所的干细胞生物学家 Nicolas Rivron 评论道:这将极大地完善组织和器官形成的路线图,它将教会我们最基本的结构,最终形成完整器官所必需的最小元素,单单这些就是无价的。

器官移植和伦理问题

不仅如此,除了基础研究之外,这项工作在“人造器官”移植领域也有广阔的应用前景。想象一下,当下一个患有白血病患者需要骨髓移植才能生存,但在未来,科学家们可以直接从病人身上获得皮肤细胞,然后将其恢复为干细胞,并在该团队创建的“人造子宫”中培养,就能获得一大群骨髓干细胞移植给病人,而不必等待可能永远不会出现的供体匹配。

Jacob Hanna 教授表示:现在谈人造器官还早,但我们真的在开拓领域,更认真地探索这些可能性,我们正在从科幻小说走向科学。

研究模式图

但令人担忧的是,“合成胚胎”和“人造子宫”也带来了伦理学上的问题,如果这项技术走向成熟并开始应用于孕育工程,未来的人类社会又会变成什么样子,是否还会有父亲、母亲和家庭的概念?亲缘关系的纽带是否就不复存在?

当然,从当前来看,这些顾虑显然是杞人忧天,人类的妊娠期要远长于小鼠,孕育过程也更加复杂,想要通过“合成胚胎”和“人造子宫”生产“新人类”,还有很长一段路要走,而且在伦理上也不会被通过。

正如凯斯西储大学医学院的发育生物学家 Paul Tesar 所说:随着我们不断革新干细胞来源的胚胎的生物技术,合成胚胎和自然胚胎的界线也来越模糊,灰色地带总是存在的,但作为科学家和整个社会,我们需要团结起来,决定界限在哪里,并定义什么是道德上可以接受的。

 

参考文献:

1.https://www.cell.com/cell/fulltext/S0092-8674(22)00981-3
2. https://doi.org/10.1016/S0140-6736(20)30677-2
3.https://www.nature.com/articles/s41586-021-03416-3
4.https://www.statnews.com/2022/08/01/synthetic-mouse-embryos-created-from-stem-cells-without-sperm-eggs-uterus/

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    2022-11-30 liye789132251
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    2023-03-08 维他命
  4. [GetPortalCommentsPageByObjectIdResponse(id=1885934, encodeId=80e6188593402, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Nov 30 23:52:49 CST 2022, time=2022-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872484, encodeId=8eff18e248404, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Aug 29 23:52:49 CST 2022, time=2022-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962813, encodeId=b0a5196281320, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Mar 08 10:52:49 CST 2023, time=2023-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1238170, encodeId=50f212381e02f, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29338272806, createdName=ms2000001752510250, createdTime=Thu Aug 11 23:33:56 CST 2022, time=2022-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315490, encodeId=0f4a131549097, content=<a href='/topic/show?id=6fcc83e0554' target=_blank style='color:#2F92EE;'>#胚胎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83705, encryptionId=6fcc83e0554, topicName=胚胎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Wed Aug 10 22:52:49 CST 2022, time=2022-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1522343, encodeId=eff915223434a, content=<a href='/topic/show?id=d36d3681414' target=_blank style='color:#2F92EE;'>#卵子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36814, encryptionId=d36d3681414, topicName=卵子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73f511449037, createdName=zlawrance, createdTime=Wed Aug 10 22:52:49 CST 2022, time=2022-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620118, encodeId=86fb162011866, content=<a href='/topic/show?id=581624e8522' target=_blank style='color:#2F92EE;'>#人工合成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24785, encryptionId=581624e8522, topicName=人工合成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=151120073605, createdName=循证小兵, createdTime=Wed Aug 10 22:52:49 CST 2022, time=2022-08-10, status=1, ipAttribution=)]
    2022-08-11 ms2000001752510250

    学习

    0

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    2022-08-10 ailian1202
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    2022-08-10 zlawrance
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