Lab-Grown Human Brain Organoids Go Animal-Free

Summary: Researchers have innovated a method to produce lab-grown mini brains, known as human brain organoids, free of animal cells, promising a more accurate study and treatment of neurodegenerative conditions.

Previously, brain organoids were grown using a substance derived from mouse sarcomas called Matrigel, leading to inconsistencies due to its undefined composition and variability. The new method uses an engineered extracellular matrix free of animal components, improving the neurogenesis of brain organoids.

This breakthrough allows for more accurate replication of human brain conditions and could open doors for personalized treatment of neurodegenerative diseases such as ALS and Alzheimer’s.

Key Facts:

  1. The new brain organoids are grown using an engineered extracellular matrix without animal components, overcoming the previous method’s variability issues.
  2. The lab-grown organoids using this new method showed enhanced neurogenesis compared to previous studies.
  3. This method allows for potential reprogramming with cells from patients suffering from neurodegenerative diseases, paving the way for personalized treatments.

Source: University of Michigan

Researchers at University of Michigan developed a method to produce artificially grown miniature brains — called human brain organoids — free of animal cells that could greatly improve the way neurodegenerative conditions are studied and, eventually, treated.

Over the last decade of researching neurologic diseases, scientists have explored the use of human brain organoids as an alternative to mouse models.

This shows a brain in a dish.
That method suffers significant disadvantages, with a relatively undefined composition and batch-to-batch variability. Credit: Neuroscience News

These self-assembled, 3D tissues derived from embryonic or pluripotent stem cells more closely model the complex brain structure compared to conventional two-dimensional cultures.

Until now, the engineered network of proteins and molecules that give structure to the cells in brain organoids, known as extracellular matrices, often used a substance derived from mouse sarcomas called Matrigel.

That method suffers significant disadvantages, with a relatively undefined composition and batch-to-batch variability.

The latest U-M research, published in Annals of Clinical and Translational Neurology, offers a solution to overcome Matrigel’s weaknesses.

Investigators created a novel culture method that uses an engineered extracellular matrix for human brain organoids — without the presence of animal components – and enhanced the neurogenesis of brain organoids compared to previous studies.

“This advancement in the development of human brain organoids free of animal components will allow for significant strides in the understanding of neurodevelopmental biology,” said senior author Joerg Lahann, Ph.D., director of the U-M Biointerfaces Institute and Wolfgang Pauli Collegiate Professor of Chemical Engineering at U-M.

“Scientists have long struggled to translate animal research into the clinical world, and this novel method will make it easier for translational research to make its way from the lab to the clinic.”

The foundational extracellular matrices of the research team’s brain organoids were comprised of human fibronectin, a protein that serves as a native structure for stem cells to adhere, differentiate and mature. They were supported by a highly porous polymer scaffold.

The organoids were cultured for months, while lab staff was unable to enter the building due to the COVID 19-pandemic.

Using proteomics, researchers found their brain organoids developed cerebral spinal fluid, a clear liquid that flows around healthy brain and spinal cords. This fluid more closely matched human adult CSF compared to a landmark study of human brain organoids developed in Matrigel.

“When our brains are naturally developing in utero, they are of course not growing on a bed of extracellular matrix produced by mouse cancer cells,” said first author Ayşe Muñiz, Ph.D., who was a graduate student in the U-M Macromolecular Science and Engineering Program at the time of the work.  

“By putting cells in an engineered niche that more closely resembles their natural environment, we predicted we would observe differences in organoid development that more faithfully mimics what we see in nature.”

The success of these xenogeneic-free human brain organoids opens the door for reprogramming with cells from patients with neurodegenerative diseases, says co-author Eva Feldman, M.D., Ph.D., director of the ALS Center of Excellence at U-M and James W. Albers Distinguished Professor of Neurology at U-M Medical School.

“There is a possibility to take the stem cells from a patient with a condition such as ALS or Alzheimer’s and, essentially, build an avatar mini brain of that patients to investigate possible treatments or model how their disease will progress,” Feldman said.

“These models would create another avenue to predict disease and study treatment on a personalized level for conditions that often vary greatly from person to person.”

Additional authors include Tuğba Topal, Ph.D., Michael D. Brooks, Ph.D., Angela Sze, Do Hoon Kim, Jacob Jordahl, Ph.D., Joe Nguyen, Ph.D., Paul H. Krebsbach, D.D.S., Ph.D., Masha G. Savelieff, all of University of Michigan.

A.J.M. is funded by the National Science Foundation with grant no. DGE 1256260. E.L.F. thanks the Robert and Katherine Jacobs Health Environmental Initiative Fund, the Andrea and Lawrence A. Wolfe Brain Health Initiative Fund, Robert E. Nederlander Sr. Program for Alzheimer’s Research, and NeuroNetwork for Emerging Therapies. We acknowledge funding from the University of Michigan Biointerfaces Institute (E.L.F. and J.L.).

About this neuroscience research news

Author: Noah Fromson
Source: University of Michigan
Contact: Noah Fromson – University of Michigan
Image: The image is credited to Neuroscience News

Original Research: Open access.
Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells” by Joerg Lahann et al. Annals of Clinical and Translational Neurology


Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells


Brain organoids are miniaturized in vitro brain models generated from pluripotent stem cells, which resemble full-sized brain more closely than conventional two-dimensional cell cultures. Although brain organoids mimic the human brain’s cell-to-cell network interactions, they generally fail to faithfully recapitulate cell-to-matrix interactions. Here, an engineered framework, called an engineered extracellular matrix (EECM), was developed to provide support and cell-to-matrix interactions to developing brain organoids.


We generated brain organoids using EECMs comprised of human fibrillar fibronectin supported by a highly porous polymer scaffold. The resultant brain organoids were characterized by immunofluorescence microscopy, transcriptomics, and proteomics of the cerebrospinal fluid (CSF) compartment.


The interstitial matrix-mimicking EECM enhanced neurogenesis, glial maturation, and neuronal diversity from human embryonic stem cells versus conventional protein matrix (Matrigel). Additionally, EECMs supported long-term culture, which promoted large-volume organoids containing over 250 μL of CSF. Proteomics analysis of the CSF found it superseded previous brain organoids in protein diversity, as indicated by 280 proteins spanning 500 gene ontology pathways shared with adult CSF.


Engineered EECM matrices represent a major advancement in neural engineering as they have the potential to significantly enhance the structural, cellular, and functional diversity that can be achieved in advanced brain models.

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  1. I really hope they do rigorous testing to make sure they aren’t aware and thinking. The idea of taking stem cells from a patient and growing a “model” brain – I know it’s different, but it makes me think of that Ewan McGregor movie with the clone island. If it’s a self-assembled brain, tiny and malformed or not, then how aware is it?

    Side note, good god these people commenting about these being aborted fetus brains really need to go back to school, read a medical textbook, or shut the hell up with how ignorant they are. Jesus. They aren’t aborted fetuses. Even if they were, we do scientific research on corpses all the time. Chill out.

  2. Simply put, if there is neural activity in this tissue, then it is alive. No philosophy or ethics or morals, you are (if true) creating human cognition with zero environmental stimuli and the killing it.

  3. I have not had a nightmare since I was a ķid and I am 62 years young, my God why is man trying to become you God is that it. No I think that if they can do something good medically for us then they will become ĥistoŕiçally famous and make them and their family rich.
    Just my thoughts
    I have an idea but I do not have the money to bring it to life
    A great idea where we would not have to rely on fossil fuel

  4. They think they’re doing the right thing. But if that thing is to kill baby humans, ew. Even worse when you remove their brains and torture them, letting them develop into something that could be as self aware as a newborn. I wish I could bundle of these up and save them humanely. Children deserve love and compassion, not this. This is disgusting. This is science fiction level horror. This is Frankenstein level absurdity. Ew.

    We’re gonna go too far one day. We’re gonna go so far that maybe we will create zombies from the unborn. Zombie babies that see what we’ve done to them and are out for vengeance. You took their brain, why won’t they take yours? Playing God always has God-level consequences. Sooner or later, they’re gonna find out. Shut down this absurdity before it’s far, far too late. Stop it. Stop it right now.

    1. They are not killing babies and removing their brains, for goodness sake. Researchers are using stem cells to create brain models in a petri dish. They can take skins cells from their own bodies and convert the stem cells into other functional cells, even brain cells.

      No one is creating zombies, or piecing parts of bodies together to create a Frankenstein’s monster. The creations are simply cells and systems that have neurological elements in a dish and using those for research purposes. No one is removing a brain, putting it in a lab and zapping it for fun or gimmicks.

      I don’t know if people are reading the title and simply commenting without reading the actual article or what, but some of these comments are total nonsense.

      1. Lmao, I agree. Think they’re just talking to be heard. Me? I’m a big sci-fi guy so this is actually kinda cool. Scary in a way but still cool. My thought would be to make an actual avatar like brain and if possible transfer the consciousness of sick person into it. Or use it to repair damaged nerves or spine.

  5. Seems these researchers have cracked the code for generation or regeneration of brain cells. Could the technique be exploited (or modified as needed) to regenerate human spinal cord core cells and sheath cells to form functional bridges to replace damaged or absent human spinal cord structures?

  6. This is what is happening to those that get aborted. They aren’t dead but they are taken apart and tested on by their fellow human. They have their brain grow in a dish, their consciousness not understood while it sits in a lab betrayed by there mother and father and fellow humans just to be tested on. Just know that none these poor souls they play god with came from those doing the testing, they came from poor people who don’t understand the value of life and have no idea what is happening to their own flesh and blood and the child that could have been is now taken apart and allowed to grow in a petri dish in a lab in the name of “science”. But it’s okay because these people wear clean white coats and have of paper in a frame with their name on it above a desk…I’m not religious but my god, the devils are among us….and they know not what they do

    1. Your comment is far from factual. So far from factual that it’s completely incorrect.

      This is fetal tissue. Tissue. It’s not a sentient, conscious being at all, it’s simply tissue like kidney tissue or liver tissue. You would not say that tissue is conscious, would you? It’s the same for fetal tissue. Additionally, it’s the stem cells that are used. Stem cells are not conscious. They are simply genetic material.

      A “child” or “baby” is not being killed or experimented on, it’s simply just stem cells and tissue. By products that would otherwise go to waste following a termination.

      Here’s the point. Abortions happen. Would you rather the “baby” (stupid to dive down to that level, but okay) be discarded, or would you rather that tissue/genetic material be put to use to help cure diseases that affect living, breathing human beings, including infants who would quite literally die without such findings that have been produced using stem cell models?

      And yes, you are spewing religious dogma.

      1. I completely agree with your response to the one spewing religious dogma! That person obviously sees an article and without fully understanding what it means or what’s going on and without doing their own research spits out some hypocritical b.s. and in turn probably doesn’t realize how that person isn’t really sticking up for those aborted babies.. but rather saying they would rather see those aborted babies sitting in a dumpster instead of turning something negative into a positive! I am not for or against abortions… I don’t understand it well enough to be able to argue one way or the other. I know friends who have done it and they have mixed views on it still. But in my mind…if it’s going to happen.. which it is regardless of what the laws say.. I’d want my aborted baby to still have the chance of helping another human being in anyway possible then have it thrown in a dumpster and forgotten about while some idiot argues that it’s not right while doing nothing about it and obviously has had no education on the matter in the first place! The reason why this hits home to me is because I have an identical twin sister who was born with a very rare eye disease and is completely blind. There is no way her eyes can be transplanted because doctors haven’t been able to figure out how to keep the optical nerve alive after it’s been cut from the brain. This kind of research IS the only way doctors will be able to hopefully one day make that discovery! So to the one spewing religious dogma…. Shut the hell up and actually do your own research BEFORE you think you have something intelligent to argue about!! Thank you Neuroscience News.. you couldn’t have said it any better!

      2. Do we know for a fact that the brains grown using this method are not sentient? Just curious, because if it’s grown from the same cells that would grow a real one it would at least try to become sentient since that’s how the cells are programmed. Not throwing shade just genuinely curious if anything shows up on the activity scan. It’s definitely valuable science but it is a little bit of a moral question since it’d be pretty ass of an existence to be the thing in that petri dish lol.

        1. I’d say, generally speaking, no organoid model is a complete brain as of yet. Most are models of one, or a few interconnecting areas and thus would not be able to achieve sentience. If a model were created with specific pain receptors and give a pain response, you still couldn’t call it sentient because it would have no concept of what pain is. Are they able to develop emotion? No because emotion is a result of experience and a general sense of consciousness. They are simply a collection of cells. However, some researchers are debating the concept of “personhood” in relation to organoids. Then again, if we go down that slope, we could theoretically debate the “personhood” of any type of growth, both within a dish or a body, if we are cynical enough to.

          In terms of activity, yes it can be generated. Then again, so can a brain slice from a dead rat generate activity in electrophysiology experiments. Is a piece of a dead rat brain exposed to chemicals sentient? It’s an interesting question, but I’d say no.

    2. I’d assumed these embryos and brains were grown from zygotes donated to science leftover from people’s IVF treatment or from donor egg and donor sperms cells. Either way, I’m sure the Mothers of these organisms would never consent to this inhumanity, if only they knew this was happening.

  7. You can’t make something out of nothing. If this article is deemed true, these scientists are essentially creating homunculus (or parts of) and philosopher stones.

  8. Ok, y’all need to stop F’n around with Krang like that before y’all find out. Just go ahead and plop him back in the stomach of his robot, point him in the direction of the Technodrome and hope he makes it back to Dimension X, otherwise Shredder is gonna come looking…

  9. Before you consider the potential for research read the first paragraph again

    “These self-assembled, 3D tissues derived from embryonic or pluripotent stem cells more closely model the complex brain structure compared to conventional two-dimensional cultures.”

    “Self-assembled” – you mean living, growing.

    “Derived from embryonic” – from human embryos.

    Growing a live human brain on it’s own for goodness knows how long with no other bodily organs is horrific. How do the scientists working on this not get traumatised from doing this?

    1. This is indeed horrific. If it is indeed a living brain. It has to know it doesn’t have a body and knows it is messed up just like the scientists who did this. Their brains are all messed up and as usual scientists wanna say hey look what we did. But even they had to use an aborted human embryo to do this proving God creates the World. Evolution does not exist only evillution

    2. My exact thoughts, one giant step for medical scientific research. One nightmare of what this really means, are we harvesting tissue for AI to inhabit vessels? 😱 And oh my god, does that lab created organic brain have a soul since it is derived from embryonic tissues? Is this now a clone start of the embryo? My meek, traditionally inspired brain cannot fathom!

    1. Thank you both for giving voice to this. Have so many lost their conscience?

    2. The entire moral of Frankenstein deals with how we need to be better caretakers or parents of our science projects. Otherwise they might come back to haunt us to the point of total destruction.

      If it is a full replica of a human brain then it is probably aware and thinking to some degree but without perception.

      they probably were also tracking neuron activity in whatever experiments they were running.

      That data would be helpful in determining the ethics of the situation.

      Long story short.

      If the brain activity is low or almost nill, it’s not aware enough to be considered conscious but on the other hand if it has similar levels of activity to the brains still inside our skulls, then it is indeed aware and probably conscious and this turns into an elderitch horror situation.

      In either case very cool and almost sci Fi in nature.
      I’m excited to see any developments in this.

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