Tag Archives: brain organoids

Organoids with four different types of brain cells from the University of Saskatchewan (USask)

While a USask-designed “mini-brain” synthetic organoid might look like a tiny wad of chewing gum, it could be a gamechanger for Alzheimer’s research (credit: USask/David Stobbe)

A May 14, 2024 news item on ScienceDaily announces research from the University of Saskatchewan that could improve diagnosis and treatment for Alzheimer’s disease,

Using an innovative new method, a University of Saskatchewan (USask) researcher is building tiny pseudo-organs from stem cells to help diagnose and treat Alzheimer’s.

When Dr. Tyler Wenzel (PhD) first came up with the idea of building a miniature brain from stem cells, he never could have predicted how well his creations would work.

Now, Wenzel’s “mini-brain” could revolutionize the way Alzheimer’s and other brain-related diseases are diagnosed and treated.

“Never in our wildest dreams did we think that our crazy idea would work,” he said. “These could be used as a diagnostic tool, built from blood.”

A May 14, 2024 University of Saskatchewan news release (also on EurekAlert), which originated the news item, provides more technical details, Note: A link has been removed,

Wenzel, a postdoctoral fellow in the College of Medicine’s Department of Psychiatry, developed the idea for the “mini-brain” – or more formally, a one-of-a-kind cerebral organoid model – while working under the supervision of Dr. Darrell Mousseau (PhD).

Human stem cells can be manipulated to develop into practically any other cell in the body. Using stem cells taken from human blood, Wenzel was able to create a tiny artificial organ – roughly three millimetres across and resembling visually what Wenzel described as a piece of chewed gum someone has tried to smooth out again.

These “mini-brains” are built by creating stem cells from a blood sample, and then transforming these stem cells into functioning brain cells. Using small synthetic organoids for research is not a novel concept – but the “mini-brains” developed in Wenzel’s lab are unique. As outlined in Wenzel’s recent published article in Frontiers of Cellular Neuroscience, the brains from Wenzel’s lab are comprised of four different types of brain cells while most brain organoids are comprised of only neurons.

In testing, Wenzel’s “mini-brains” more accurately reflect a fully-fledged adult human brain, so they can be used to more closely examine neurological conditions of adult patients, such as Alzheimer disease.

And for those “mini-brains” created from the stem cells of individuals who have Alzheimer’s, Wenzel determined that the artificial organ displayed the pathology of Alzheimer’s – just on a smaller scale.

“If stem cells have the capacity to become any cell in the human body, the question then came ‘could we create something that resembles an entire organ?’” Wenzel said. “While we were developing it, I had the crazy idea that if these truly are human brains, if a patient had a disease like Alzheimer’s and we grew their ‘mini-brain,’ in theory that tiny brain would have Alzheimer’s.”

Wenzel said this technology has the potential to change the way health services are provided to those with Alzheimer’s, particularly in rural and remote communities. This groundbreaking research has already received support from the Alzheimer Society of Canada.

If Wenzel and his colleagues can create a consistent way to diagnose and treat neurological conditions like Alzheimer’s using only a small blood sample – which has a relatively long shelf life and can be couriered – instead of requiring patients to travel to hospitals or specialized clinics, it could be a tremendous resource savings for the healthcare system and a burden off of patients.

“In theory, if this tool works the way we think it does, we could just get a blood sample shipped from La Loche or La Ronge to the university and diagnose you like that,” he said.

The early proof-of-concept work on the “mini-brains” has been extremely promising – which means the next step for Wenzel is expanding the testing to a larger pool of patients.

The researchers are also interested in trying to expand the scope of the “mini-brain” research. According to Wenzel, if they can confirm the “mini-brains” accurately reflect other brain diseases or neurological conditions, they could potentially be used to speed up diagnoses or test the efficacy of drugs on patients.

As an example, Wenzel pointed to the substantial wait times to see a psychiatrist in Saskatchewan. If the “mini-brains” could be used to test which antidepressant works best on a patient suffering from depression, it could dramatically reduce the time required to see a doctor and receive a prescription.

A former high school science teacher who made the move into the world of research and academia, Wenzel said it’s the “nature of research” to come up with a hypothesis and hit close to the mark in an experiment that excites him his work.

The astounding success of the early “mini-brains,” however, has been so staggering that Wenzel admitted he still struggles to wrap his own brain around it.

“I’m still in disbelief, but it’s also extremely motivating that something like this happened,” Wenzel said. “It gives me something that I think will impact society and have actual relevance and create some change … it has a strong potential to shift the landscape of medicine.”

Here’s a link to and a citation for the paper,

Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms by Tyler J. Wenzel, Darrell D. Mousseau. Front. Cell. Neurosci., Volume 18 – 2024 DOI: https://doi.org/10.3389/fncel.2024.1383688 Published: 08 May 2024

This paper is open access.

Artificially-grown mini-brains (organoids)—without animal components— offer opportunities for neuroscience

There’s a good (brief) description of how these fibres become organoids in the photo caption,

Engineered extracellular matrices composed of fibrillar fibronectin are suspended over a porous polymer framework and provide the niche for stem cells to attach, differentiate, and mature into organoids. Credit: Ayse Muñiz Courtesy: Michigan Medicine – University of Michigan

A July 13 ,2023 University of Michigan (Michigan Medicine) news release by Noah Fromson (also on EurekAlert) announces ‘kinder, gentler’ brain organoids. Coincidentally, these organoids more closely resemble human brains, Note: Links have been removed,

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. 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.”

Here’s a link to and a citation for the paper,

Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells by Ayşe J. Muñiz, Tuğba Topal, Michael D. Brooks, Angela Sze, Do Hoon Kim, Jacob Jordahl, Joe Nguyen, Paul H. Krebsbach, Masha G. Savelieff, Eva L. Feldman, Joerg Lahann. Annals of Clinical and Translational Neurology DOI: https://doi.org/10.1002/acn3.51820 First published: 07 June 2023

This paper is open access.

12th World Conference of Science Journalists in Medellín, Colombia from March 27-31, 2023

I very rarely get a chance to feature science from Latin America and the Caribbean, largely due to my lack of Spanish, Portuguese, or Dutch language skills. So, you might say I’m desperate to find something, which explains, at least in part, why I’m posting about the 12th World Conference (WCSJ).

A March 29, 2023 WCSJ press release (also on EurekAlert but published March 28, 2023) describes the opening day of the 2023 conference,

The opening day [March 27, 2023] of the World Conference of Science Journalists (WCSJ) 2023 in Medellín, Colombia saw hundreds of journalists from 62 countries come together in the stunning setting of the city’s Jardin Botanico.

Over 500 attendees will gather over three days to discuss science journalism, to challenge ideas and to reinforce their professional networks and friendships. 

The day began with a keynote on biodiversity delivered by Brigitte Baptiste, a Colombian biologist and expert in biodiversity issues. And it closed with an opening ceremony and vibrant social event for attendees.

Both took place under open skies in the Jardin’s orquideorama, an open air meshwork of flower-tree structures surrounded by trees, butterflies and with a backdrop of birdsong. 

Two other plenaries focused on scientific advice and news from Amazonia. The morning’s parallel panels covered Latin American and international collaboration, with discussions from Latin American women researchers, reporting on science, health and the environment in the region and what the world can learn from Latin American and the Caribbean early warning alerts systems. The afternoon saw discussions on COVID-19, popular science writing and astronomy. 

The conference continues until Friday when there are scientific tours and excursions that provide the opportunity to visit local research teams and find out more about science in the region.

According to WWF, Colombia is the most biodiverse country per square kilometre in the world. It is also the country with the largest number of bird species — over 1,900  —  and the greatest number of butterfly species — over 3,600 or 20% butterfly species. 

Milica Momcilovic, President of the World Federation of Science Journalists said: “Independent journalism is the lifeblood of democracy and our focus at the Federation is, and will continue to be, supporting independent science journalism around the world. I have seen first hand how talented science journalists can change the world for the better and during this conference they will tell us these stories in person.”

Ximena Serrano Gil, Director of the Medellín conference said: “Colombia and Medellin are a biodiversity hotspot, an unrivalled laboratory for helping other nations adapt to climate change, a model for how to feed populations in rapidly changing tropical environments, and a cultural repository where thousands of years of indigenous peoples’ knowledge can make a lasting contribution to the wisdom of future generations.”

She continued: “The opportunity to share ideas and collaborate with others is invaluable and we must continue to create platforms that facilitate these interactions. I hope that other places in the global south will have the opportunity to host the WCSJ.” 

Over the past two decades, the World Federation of Science Journalists (WFSJ) has mounted the WCSJ every other year. The event has been held in cities across the globe, and the current edition in Medellín, Colombia, was postponed from 2021 because of the COVID-19 pandemic. Each gathering lasts about a week and attracts hundreds of participants from the WFSJ membership, including some 10,000 science writers in 51 countries.

This conference has been put together with a specific focus on the global south and on amplifying new voices from science journalist communities.

The programme has something that interests me, a talk on brain organoids according to a March 17, 2023 WCSJ press release, Note: Links have been removed,

Food security, organoid intelligence, local tours and scientific excursions

Plenary: Challenges to food security in the face of global catastrophe risks

In times of crisis and global risks, very few issues have as many factors feeding into them as food security. The integrative measures envisaged by various global players link the actions that are needed to meet the challenges we face. These should be considered in terms of technology, economics and security to ensure the future of food security, but also how science validates the environmental the environmental impact and guarantees the viability of the processes. 

Jennifer Wiegel is the Sub Regional Manager for Central America and a scientist in the Food Environment and Consumer Behavior research area of the Alliance of Bioversity International and CIAT [International Center for Tropical Agriculture]. Her research includes work on agri-food systems, food markets and value chains for inclusion and sustainability and public procurement. She has a Ph.D. in Sociology from the University of Wisconsin-Madison and a Master’s in Rural Sociology from the same University.

Juan Fernando Zuluaga is the National Territorial Coordinator for Antioquia. He has a  PhD in Social Sciences from the University of Antioquia and a Master in RuralEconomics from the Federal University of Ceará-Brazil. Juan is a specialist in finance from  the Latin American Autonomous University and Agricultural Engineer from the National University of Medellín.

Thomas Hartung, MD, PhD. Professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health and Whiting School of Engineering and Professor for Pharmacology and Toxicology at University of Konstanz, Germany. He is leading the revolution in toxicology to move away from 50+ year old animal testing to organoid cultures and the use of artificial intelligence.

New keynote

Climate change: How to embroider the risks that put the stability of the most vulnerable at risk

Paola Andrea Arias Gómez is Professor of the Environmental School of the Faculty of Engineering of the University of Antioquia. In 2021 she was El Espectador’s Person of the Year and received the Medellin Council’s Orchid Award for Scientific Merit.

Paola completed her undergraduate studies in Civil Engineering and a Master’s degree in Water Resources Development at the National University of Colombia, Medellin. She was Head of the Environmental School of the Faculty of Engineering of the University of Antioquia and is now a member of the First Working Group of the Intergovernmental Panel on Climate Change (IPCC). She is also a member of the GEWEX Hydroclimatology Panel (GHP), the Amazon Regional Hydrogeomorphology Working Group (UNESCO) and the WCRP Science Plan Development Team (WCRP) Lighthouse Activities – My Climate Risk.

Parallel session:

In conversation: “Organoid intelligence”: the future of modern computing from human brain cells. [sic]

Biocomputing is a huge effort to compact computational power and increase its efficiency to overcome current technological limits. Researchers at Johns Hopkins delve into this technology that may one day produce computers that are faster, more efficient and more powerful than silicon-based computing and AI.

Thomas Hartung, MD, PhD. will present the team’s latest research and discuss its context, implications and what his hopes are for the field. 

Thomas Hartung is the Director of Centers for Alternatives to Animal Testing (CAAT, http://caat.jhsph.edu) of both universities. CAAT hosts the secretariat of the Evidence-based Toxicology Collaboration (http://www.ebtox.org) and manages collaborative programs on Good Read-Across Practice, Good Cell Culture Practice, Green Toxicology, Developmental Neurotoxicity, Developmental Immunotoxicity, Microphysiological Systems and Refinement.

I found another intriguing session (Story Corner: “Fusion Energy and Climate Change – The Conversation begins” by ITER) which was held on Tuesday, March 28, 2023 at 9:30 – 10:00 am during the coffee break. (For more about fusion energy, see my October 28, 2022 posting “Overview of fusion energy scene“.)

While it’s too late to sign up for the conference, you might find perusing the programme schedule provides some insight into issues being faced my science journalists outside the Canada/US bubble.

Cortical spheroids (like mini-brains) could unlock (larger) brain’s mysteries

A March 19, 2021 Northwestern University news release on EurekAlert announces the creation of a device designed to monitor brain organoids (for anyone unfamiliar with brain organoids there’s more information after the news),

A team of scientists, led by researchers at Northwestern University, Shirley Ryan AbilityLab and the University of Illinois at Chicago (UIC), has developed novel technology promising to increase understanding of how brains develop, and offer answers on repairing brains in the wake of neurotrauma and neurodegenerative diseases.

Their research is the first to combine the most sophisticated 3-D bioelectronic systems with highly advanced 3-D human neural cultures. The goal is to enable precise studies of how human brain circuits develop and repair themselves in vitro. The study is the cover story for the March 19 [March 17, 2021 according to the citation] issue of Science Advances.

The cortical spheroids used in the study, akin to “mini-brains,” were derived from human-induced pluripotent stem cells. Leveraging a 3-D neural interface system that the team developed, scientists were able to create a “mini laboratory in a dish” specifically tailored to study the mini-brains and collect different types of data simultaneously. Scientists incorporated electrodes to record electrical activity. They added tiny heating elements to either keep the brain cultures warm or, in some cases, intentionally overheated the cultures to stress them. They also incorporated tiny probes — such as oxygen sensors and small LED lights — to perform optogenetic experiments. For instance, they introduced genes into the cells that allowed them to control the neural activity using different-colored light pulses.

This platform then enabled scientists to perform complex studies of human tissue without directly involving humans or performing invasive testing. In theory, any person could donate a limited number of their cells (e.g., blood sample, skin biopsy). Scientists can then reprogram these cells to produce a tiny brain spheroid that shares the person’s genetic identity. The authors believe that, by combining this technology with a personalized medicine approach using human stem cell-derived brain cultures, they will be able to glean insights faster and generate better, novel interventions.

“The advances spurred by this research will offer a new frontier in the way we study and understand the brain,” said Shirley Ryan AbilityLab’s Dr. Colin Franz, co-lead author on the paper who led the testing of the cortical spheroids. “Now that the 3-D platform has been developed and validated, we will be able to perform more targeted studies on our patients recovering from neurological injury or battling a neurodegenerative disease.”

Yoonseok Park, postdoctoral fellow at Northwestern University and co-lead author, added, “This is just the beginning of an entirely new class of miniaturized, 3-D bioelectronic systems that we can construct to expand the capacity of the regenerative medicine field. For example, our next generation of device will support the formation of even more complex neural circuits from brain to muscle, and increasingly dynamic tissues like a beating heart.”

Current electrode arrays for tissue cultures are 2-D, flat and unable to match the complex structural designs found throughout nature, such as those found in the human brain. Moreover, even when a system is 3-D, it is extremely challenging to incorporate more than one type of material into a small 3-D structure. With this advance, however, an entire class of 3-D bioelectronics devices has been tailored for the field of regenerative medicine.

“Now, with our small, soft 3-D electronics, the capacity to build devices that mimic the complex biological shapes found in the human body is finally possible, providing a much more holistic understanding of a culture,” said Northwestern’s John Rogers, who led the technology development using technology similar to that found in phones and computers. “We no longer have to compromise function to achieve the optimal form for interfacing with our biology.”

As a next step, scientists will use the devices to better understand neurological disease, test drugs and therapies that have clinical potential, and compare different patient-derived cell models. This understanding will then enable a better grasp of individual differences that may account for the wide variation of outcomes seen in neurological rehabilitation.

“As scientists, our goal is to make laboratory research as clinically relevant as possible,” said Kristen Cotton, research assistant in Dr. Franz’s lab. “This 3-D platform opens the door to new experiments, discovery and scientific advances in regenerative neurorehabilitation medicine that have never been possible.”

Caption: Three dimensional multifunctional neural interfaces for cortical spheroids and engineered assembloids Credit: Northwestern University

As for what brain ogranoids might be, Carl Zimmer in an Aug. 29, 2019 article for the New York Times provides an explanation,

Organoids Are Not Brains. How Are They Making Brain Waves?

Two hundred and fifty miles over Alysson Muotri’s head, a thousand tiny spheres of brain cells were sailing through space.

The clusters, called brain organoids, had been grown a few weeks earlier in the biologist’s lab here at the University of California, San Diego. He and his colleagues altered human skin cells into stem cells, then coaxed them to develop as brain cells do in an embryo.

The organoids grew into balls about the size of a pinhead, each containing hundreds of thousands of cells in a variety of types, each type producing the same chemicals and electrical signals as those cells do in our own brains.

In July, NASA packed the organoids aboard a rocket and sent them to the International Space Station to see how they develop in zero gravity.

Now the organoids were stowed inside a metal box, fed by bags of nutritious broth. “I think they are replicating like crazy at this stage, and so we’re going to have bigger organoids,” Dr. Muotri said in a recent interview in his office overlooking the Pacific.

What, exactly, are they growing into? That’s a question that has scientists and philosophers alike scratching their heads.

On Thursday, Dr. Muotri and his colleagues reported that they  have recorded simple brain waves in these organoids. In mature human brains, such waves are produced by widespread networks of neurons firing in synchrony. Particular wave patterns are linked to particular forms of brain activity, like retrieving memories and dreaming.

As the organoids mature, the researchers also found, the waves change in ways that resemble the changes in the developing brains of premature babies.

“It’s pretty amazing,” said Giorgia Quadrato, a neurobiologist at the University of Southern California who was not involved in the new study. “No one really knew if that was possible.”

But Dr. Quadrato stressed it was important not to read too much into the parallels. What she, Dr. Muotri and other brain organoid experts build are clusters of replicating brain cells, not actual brains.

If you have the time, I recommend reading Zimmer’s article in its entirety. Perhaps not coincidentally, Zimmer has an excerpt titled “Lab-Grown Brain Organoids Aren’t Alive. But They’re Not Not Alive, Either.” published in Slate.com,

From Life’s Edge: The Search For What It Means To Be Alive by Carl Zimmer, published by Dutton, an imprint of Penguin Publishing Group, a division of Penguin Random House, LLC. Copyright © 2021 by Carl Zimmer.

Cleber Trujillo led me to a windowless room banked with refrigerators, incubators, and microscopes. He extended his blue-gloved hands to either side and nearly touched the walls. “This is where we spend half our day,” he said.

In that room Trujillo and a team of graduate students raised a special kind of life. He opened an incubator and picked out a clear plastic box. Raising it above his head, he had me look up at it through its base. Inside the box were six circular wells, each the width of a cookie and filled with what looked like watered-down grape juice. In each well 100 pale globes floated, each the size of a housefly head.

Getting back to the research about monitoring brain organoids, here’s a link to and a citation for the paper about cortical spheroids,

Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids by Yoonseok Park, Colin K. Franz, Hanjun Ryu, Haiwen Luan, Kristen Y. Cotton, Jong Uk Kim, Ted S. Chung, Shiwei Zhao, Abraham Vazquez-Guardado, Da Som Yang, Kan Li, Raudel Avila, Jack K. Phillips, Maria J. Quezada, Hokyung Jang, Sung Soo Kwak, Sang Min Won, Kyeongha Kwon, Hyoyoung Jeong, Amay J. Bandodkar, Mengdi Han, Hangbo Zhao, Gabrielle R. Osher, Heling Wang, KunHyuck Lee, Yihui Zhang, Yonggang Huang, John D. Finan and John A. Rogers. Science Advances 17 Mar 2021: Vol. 7, no. 12, eabf9153 DOI: 10.1126/sciadv.abf9153

This paper appears to be open access.

According to a March 22, 2021 posting on the Shirley Riley AbilityLab website, the paper is featured on the front cover of Science Advances (vol. 7 no. 12).