合成“胚胎” | Nature Podcast

来源：Nature自然科研

又到了每周一次的 Nature Podcast 时间了！欢迎收听本周由Benjamin Thompson和 Shamini Bundell 带来的一周科学故事，本期播客片段讨论建立早期胚胎模型。欢迎前往iTunes或你喜欢的其他播客平台下载完整版，随时随地收听一周科研新鲜事。

音频文本：

Host: Benjamin Thompson

First up, reporter Nick Howe has been looking into the development of embryos.

Interviewer: Nick Howe

Scientists have got a pretty good idea of what goes on during the nine months of pregnancy, but for the very early stages, like when the embryo implants into the wall of the uterus – the so-called peri-implantation stage – not much is known.

Interviewee: Amander Clark

Implantation of human embryos into the lining of the uterus is a really mysterious process. It’s very difficult to study and this just happens to be the time in embryonic development where the cell types that will ultimately become the adult cells in a body will start to specialise and differentiate, and we know very little about that process in humans.

Interviewer: Nick Howe

This is Amander Clark, a stem-cell biologist who researches early human development. To better understand this mysterious stage, scientists use two main strategies. One is to use early-stage human embryos that have come from in vitro fertilisation clinics and have been consented for use in research. But these samples are rare, and due to current ethical guidelines, these embryos cannot be grown in the lab for longer than 14 days. The second strategy is to use stem cells, specifically pluripotent stem cells, which can change or differentiate into any cell type. These can be induced to form structures like those seen in a human embryo. The trouble with this is that stem cell cultures don’t fully mimic embryo development as the cells don’t organise themselves in the same way. So, how can researchers better understand the implantation period? Well Jianping Fu, a mechanical engineer, has been looking at how mechanical and chemical signals interact with stem cells. Through these manipulations of stem cells, he found something unexpected which may help.

Interviewee: Jianping Fu

So, somehow, to our great surprise, we observed that under some engineered, three-dimensional culture environment with suitable mechanical signals, human pluripotent stem cells self-organise. Somehow in the subset of those colonies, we start to observe some very interesting asymmetrical structures and these asymmetric structures resemble the core of the peri-implantation human embryo. So, this really got us excited.

Interviewer: Nick Howe

Jianping has been working to make a system that reliably produces these embryo-like structures. This week in Nature, he presents a microfluidic system – a tiny device that precisely controls fluids and contains pores within which embryo-like structures can form.

Interviewee: Jianping Fu

Basically, this microfluidic system traps little balls of human pluripotent stem cells in such a way that you can apply chemicals to cells only on one side of the ball. The microfluidic delivery will allow control over the timing of the chemical signal. More or less, you can now control when and where the cells will be exposed to chemical signals that are important to drive them to continue to differentiate and develop.

Interviewer: Nick Howe

So, rather than producing a ball of disorganised cells, this system allows Jianping to induce the formation of organised cell structures that more closely represent a developing embryo. Specifically, it allows asymmetric development. When an embryo implants into the uterus, typically the top and bottom will differentiate differently, leading to distinctive structures. Jianping was able to replicate this in his system and do it reliably.

Interviewee: Jianping Fu

Now, using this microfluidic system and this is very controllable and reproducible and scalable, we can generate these embryo-like structures with very high efficiency – more than 95% almost.

Interviewer: Nick Howe

Amander, who you heard from earlier and who wasn’t associated with this work, thinks this system is going to provide an important tool to understand embryonic development.

Interviewee: Amander Clark

I’m very excited about the utility of this technology because it can help us to understand diseases in the reproductive population and in particular, a focus on early embryo loss which occurs with these early miscarriages, and early miscarriages can occur in a many instances of pregnancy and using these models, we can help to understand and perhaps prevent women from experiencing early embryonic loss and infertility.

Interviewer: Nick Howe

Another potential use of this technology is that it may allow researchers to use these artificial embryos to study development beyond the current 14-day limit. The cells used in this research could not go on to become humans, as they lacked some critical structures required to do so. So, the 14-day rule may not apply, meaning that these model embryos could be used to understand more about the obscure early stages of pregnancy. But, when there are such similarities between models and real embryos, it does raise ethical questions. Ethicists are divided on how the 14-day rule should be applied in these cases. I reached out to a bioethicist, Giulia Cavaliere from Lancaster University, and asked her if she thought the 14-day rule would apply to Jianping’s model. 

Interviewee: Giulia Cavaliere

So, the short answer to this question is no, it wouldn’t apply to this model, but there is, in a sense, a gap in the regulations about whether these are human embryos or not and what features of these models would make them resemble human embryos enough that the rule would apply.

Interviewer: Nick Howe

For Giulia, the interesting question is whether or not these models could replace human embryos in research altogether, especially as Jianping’s study was able to create these structures from stem cells that hadn’t come from human embryos at all. Regardless of whether or not these cell models will allow researchers to look beyond 14 days, they will help them better understand the mysterious early implantation stage of embryonic development. For example, it could be used to model the effects of drugs on an early foetus. Here’s Jianping.

Interviewee: Jianping Fu

I think it’s important for me to emphasise that this research area can lead to a lot of good. Such research is very important on the path to a better understanding of birth defects and other problems that happen in very early pregnancy. 

Host: Benjamin Thompson

That was Jianping Fu of the University of Michigan in the US. You also heard from Amander Clark of the University of California, Los Angeles, and Giulia Cavaliere of Lancaster University in the UK. You can find Jianping’s paper, along with a News and Views article written by Amander, over at nature.com.ⓝ

Nature Podcast每周为您带来科学世界的全球新闻故事，覆盖众多科研领域，重点讲述Nature期刊上激动人心的研究故事。我们将话筒递给研究背后的科学家，呈现来自Nature记者和编辑的深度分析。在2017年，来自中国的收听和下载超过50万次，居全球第二。

↓↓iPhone用户长按二维码进入iTunes订阅

 ↓↓安卓用户长按二维码进入推荐平台acast订阅

点击“阅读原文”访问Nature官网收听完整版播客