Researchers at University of Michigan (U-M) have developed a method to produce human brain organoids without animal cells that could improve the way neurodegenerative conditions are studied and treated.
Human brain organoids are derived from embryonic or pluripotent stem cells and more closely model the complex brain structure compared to conventional two-dimensional cultures.
Until now, the extracellular matrices in brain organoids often used a substance derived from mouse sarcomas called Matrigel, which has several disadvantages.
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.
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.
Using proteomics, researchers found their brain organoids developed cerebral spinal fluid (CSF), which more closely matched human adult CSF compared to human brain organoids developed in Matrigel.
“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 patient to investigate possible treatments or model how their disease will progress,” said co-author Eva Feldman, Director of the ALS Center of Excellence at U-M and James W Albers Distinguished Professor of Neurology at U-M Medical School. “These models would create another avenue to predict disease and study treatment on a personalised level for conditions that often vary greatly from person to person.”
Image shows: 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.