Healthy skepticism needed on claim of stem cell-derived human fetal brain

human fetal brain IPSCOne of the biggest claims related to stem cells and in particular to induced pluripotent stem cells (IPSC or IPS cells) of 2015 came just yesterday about growing a human fetal brain.

A press release from Ohio State University reports that two of its researchers had grown a nearly full-formed human fetal brain.

My initial reaction was, “Wow”, but a very skeptical “wow”.

A few past stem cell claims that turned out to be too good to be true have made me even more cautious and skeptical about what I read, especially if it is a sexy claim without much data.

In this case, the work has not been published. We need to learn more before we can be sure about this fetal brain claim so it’s no time for hype.

The story was picked up like wildfire by the media. That’s the danger with science communication by press release. Maybe it really is a nearly fully formed fetal human brain grown from IPSC in a dish (see image above) or maybe it isn’t.

Update: For some background on solid, organoid, mini-brain stuff, I recommend this.

Professor Rene Anand and colleague Susan McKay reportedly did this newly reported work, and presented it at the 2015 Military Health System Research Symposium in Florida. I was unable to find a copy of the presentation or abstract, which would have been helpful. Without more data, the structure shown in the above image could be just about anything. That’s the thing with organoids; from the outside they don’t look like much.

The Ohio State PR says that Anand is somewhat new to stem cells and yet was able to grow this nearly fully formed fetal human brain.  That would be a rare and impressive accomplishment.

They apparently used an organoid-type approach that is apparently being patented and is proprietary, which also makes it hard to evaluate. An important focus seems to be on commercialization:

“Anand and McKay are co-founders of a Columbus-based start-up company, NeurXstem, to commercialize the brain organoid platform, and have applied for funding from the federal Small Business Technology Transfer program to accelerate its drug discovery applications.”

In addition to analysis by microscopy they reportedly did some kind of gene expression analysis to make the claim that the IPSC fetal brain expresses 99% of the expected genes. I’d like to learn more about that. More from the PR:

“High-resolution imaging of the organoid identifies functioning neurons and their signal-carrying extensions – axons and dendrites – as well as astrocytes, oligodendrocytes and microglia. The model also activates markers for cells that have the classic excitatory and inhibitory functions in the brain, and that enable chemical signals to travel throughout the structure.”

In principle these kinds of analyses would indeed help to identify this tissue as brain-like in nature. Let’s wait and see the data. There is no patent application in the public domain on this that I could find at least, which is too bad as that could have provided more information too.

I also wondered about ethical issues of making a fetal brain. At some point could it start to think? Anand is not concerned according to The Guardian:

“The ethical concerns were non-existent, said Anand. “We don’t have any sensory stimuli entering the brain. This brain is not thinking in any way.”

You sure about that? Have they talked to a bioethicist?

The Guardian reporter Helen Thomson deserves a hat tip on this story. She really did the needed homework on this one unlike the other media stories I found and she reached out to independent scientists who formed a consensus that we can’t be sure of this claim:

Several researchers contacted by the Guardian said it was hard to judge the quality of the work without access to more data, which Anand is keeping under wraps due to a pending patent on the technique. Many were uncomfortable that the team had released information to the press without the science having gone through peer review.

Zameel Cader, a consultant neurologist at the John Radcliffe Hospital, Oxford, said that while the work sounds very exciting, it’s not yet possible to judge its impact. “When someone makes such an extraordinary claim as this, you have to be cautious until they are willing to reveal their data.”

On this and other similar cool science claims made by press release, the best approach is to employ a healthy dose of skepticism. Of course an antidote to skepticism is rigorous peer-reviewed data.

5 thoughts on “Healthy skepticism needed on claim of stem cell-derived human fetal brain”

  1. Michael Finfer, MD

    Maybe I am getting stuck on the word “fetal.” An embryo becomes a fetus at about the time the mother can feel its movements. To just the phrase “fully formed fetal brain” suggest to me a size that makes the claim almost unbelievable.

    Is that perhaps the source of my confusion?

  2. Michael, the lack of blood supply is actually the main reason these organoids can only reach a limited developmental stage. In this case the development halts at the equivalent of a 5 week old human brain due to the lack of blood supply.

  3. Michael Finfer, MD

    I wonder how it is possible to grow a “fully formed” brain-like structure without a blood supply. Such a structure would be too big for nutrients and oxygen to diffuse in in adequate amounts. Somehow, I doubt this one.

  4. Totally agree with you on this one. Read the press release as well today and I tried to find whether this was published, but couldn’t find anything. They’re certainly not the first to develop an organoid-based minibrain and we’ll need to see more data before they can righteously claim that it is an 11-week old fetal brain in a dish. The press-release smells a little like NeurXstem advertisement…

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