Scientists at University of Michigan have engineered a method to develop artificially grown miniature brains — called human brain organoids — free of animal cells. The invention provides an alternative to mouse models and could forever revolutionize the way neurodegenerative conditions are studied and treated.
This is according to a press release by the institution published on Wednesday.
To build their new brain organoids, researchers created a novel culture method that uses an engineered extracellular matrix for human brain organoids — without the presence of animal components.
“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.”
These extracellular matrices were composed of human fibronectin, a protein that serves as a native structure for stem cells to adhere, differentiate and mature. They were further supported by a highly porous polymer scaffold.
Using proteomics, researchers found that their brain organoids developed cerebral spinal fluid, a clear liquid that flows around healthy brain and spinal cords.
“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 Ayse 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 new research brings the possibility of reprogramming with cells from patients with neurodegenerative diseases to light, said 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 in the statement.
“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.”
The study was published in Annals of Clinical and Translational Neurology.
Study abstract:
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.
