A new kind of brain organoid offers possibilities in neuroscience … – The Michigan Daily

University of Michigan researchers published a study detailing a new method for making brain organoids, or miniature lab-grown brains used in neuroscience research, last June. Previously, the most common method for creating human brain organoids relied on Matrigel — a substance made of cells from mouse sarcomas — to provide structure for the organoids, but the new method uses an engineered extracellular matrix composed of human-derived proteins.

The lack of cells from other species in the new organoids means they more closely resemble actual human brains, opening up research possibilities on neurodegenerative diseases such as Alzheimer’s and Parkinson’s. U-M alum Ayse Muñiz, who worked on the research as part of her Ph.D. thesis while at the University, said in an interview with The Michigan Daily that having organoids with only human cells is advantageous for translational research — the process of turning knowledge from lab research into something with real-world applications.

“When you’re doing translational research, having contamination from other species will limit your ability to translate this into the clinic,” Muñiz said. “The presence of other species basically elicits immunogenic responses, and can just be a limitation for scale and other things like that. And so here now that you’ve taken that out, it makes the path to translation a lot easier.”

The researchers created the extracellular matrix for the brain organoids by 3D printing scaffolds out of polymer material. The scaffold was coated in fibronectin solution, which solidified and was then seeded with stem sells. The brain organoids grew over a period of 215 days to have the ability to produce their own cerebrospinal fluid.

Joerg Lahann, professor of chemical engineering and director of the U-M Biointerfaces Institute, told The Daily an analysis of the spinal fluid revealed the new brain organoids were more similar to a developing brain than previous brain organoids.

“If we analyze the cerebrospinal fluid, we find that the protein composition is actually closer to what you see in a developing brain than what you would see in other organoid stocks which have been published previously,” Lahann said.

Neurology professor Eva Feldman, who also worked on the study, wrote in an email to The Daily that the extracellular matrix the researchers created lets the brain cells in each organoid interact with each other better, and more closely resembles the in situ, or natural, environment for brain cells.

“Our engineered matrices simulate the extracellular milieu, i.e., the biochemical environment surrounding cells in situ in tissue,” Feldman wrote. “Thus, our matrices enhance extracellular interactions to brain cells as the organoids form, which better mirrors development in humans than in Matrigel.”

The researchers used two sources of stem cells for the study — an embryonic stem cell source gifted by another lab at the University and an induced pluripotent stem cell source, or iPSC. According to Feldman, iPSCs can help minimize bioethical concerns regarding stem cells because they are sourced from adult patients who provide informed consent for the cell usage. Feldman said the method for getting these cells involves retrieving skin cells from adult patients and deprogramming the cells so they act like stem cells.

“iPSCs are generated from skin biopsy from adult humans,” Feldman wrote. “The skin cells are wiped clean of their ‘skin identity’ deprogramming them into stem cell-like iPSCs. These iPSCs are then reprogrammed into the various brain cells over the course of brain organoid formation.”

The ability to obtain stem cells from individual patients means it is possible to create mini-brains specific to both patients with neurodegenerative diseases and those with healthy brains. Feldman wrote that comparing these two kinds of brain organoids could give scientists a closer understanding of the progression of different neurodegenerative diseases.

“(Making these organoids) allows us to study brain organoid biology within the genetic context of neurodegenerative diseases, because the cells come from patients,” Feldman wrote. “We then compare these ‘disease’ brain organoids to control organoids generated from healthy individuals and the difference between them to shed insight into disease biology.”

The ability to create brain organoids specific to different situations means scientists can study how different factors will affect how a brain will respond to various drug treatments. Lahann gave an example of using biochemical factors to simulate the effects of exercise on in vitro brain organoids created from the cells of a patient with Parkinson’s disease.

“You could do things like ask questions (such as) how does exercise affect certain treatment in those brain organoids?” Lahann said. “That doesn’t mean that the (mini) brain is having exercise, but we know what factors we would give … so we could ask questions about the interplay between drugs and exercises on Parkinson’s, for instance.”

Lahann said he believes brain health and diseases will be the next major research area in an aging society, and brain organoids offer researchers a way to study things about the brain that can be hard to study without this technology.

“I think brain health and brain diseases is going to be absolutely the next frontier, and we don’t know much,” Lahann said. “We can’t see into the brain. We don’t have good access to it. We don’t have good animal models for it. What we desperately need is better ways to understand the disease … And for that, we need models such as the mini brains, this is just one way to do it.”

Muñiz emphasized that while brain organoid research has a long way to go before reaching its full potential, the organoids are promising due to their ability to let researchers study tissues from human cells without having to use actual human tissue.

“It’s very difficult to get human brain tissue, for good reason,” Muñiz said. “This offers an exciting way to ask questions that there’s really no other way to ask, and potentially leverage them for developing drugs so that they are safer or have a higher probability of success and are more translatable (into medical practice).”

Summer News Editor Abigail VanderMolen can be reached at [email protected].

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Lucas Leclerc

Tel un mélodiste des pixels, je suis Lucas Leclerc, un Compositeur de Contenus Digitaux orchestrant des récits qui fusionnent la connaissance et l'imagination. Mon passage à l'Université Catholique de Lyon a accordé une symphonie à ma plume. Telle une partition éclectique, mes écrits se déploient des arcanes de la sécurité internationale aux méandres de la politique, des étoiles de la science aux prédictions des bulletins météo. Je navigue entre les lignes avec la même aisance qu'un athlète soucieux de sa santé. Chaque article est une note de transparence, une mélodie d'authenticité. Rejoignez-moi dans cette composition numérique où les mots s'entremêlent pour former une toile captivante de connaissances et de créativité, où la sécurité mondiale danse avec les étoiles, où les sphères politiques se fondent avec la météorologie, et où chaque paragraphe est une sonate pour la compréhension globale.

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