Stanford scientists report using stem cells to create 3D spheroids of the oligodendrocytes, neurons and astrocytes key to myelin-wasting diseases like MS.
Stem cells tweaked in the laboratory have allowed researchers, reportedly for a first time, to generate and maintain ball-shaped cultures — called spheroids — of human brain cells in 3D that contain oligodendrocytes, the cells that produce myelin, along with neurons and the astrocytes that are essential to nerve cell health.
These long-surviving spheroids (which the researchers call “human oligodendrocyte spheroids”) will help scientists in studying how oligodendrocytes develop and interact with other brain cells, and what happens when they lose the ability to regenerate myelin — the protective coating on nerve cell fibers that promote cell-to-cell communication. Myelin’s loss, called demyelination, marks diseases like multiple sclerosis (MS).
The study “Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures” was published in the journal Nature Neuroscience.
Understanding how oligodendrocytes work and interact with other brain cells, such as neurons or astrocytes, is vital to developing therapies that might halt or even prevent diseases like MS. Of note, astrocytes are a group of star-shaped cells that provide neurons with energy, and work as a platform to clean up their waste; other functions they perform within the brain include regulating blood flow and inflammation.
While human nerve cells revealed many of their secrets years ago, those of human oligodendrocytes are still far from known. Not only do they appear late in brain development, but they’ve also been much more challenging to study in the lab (in vitro). And, as the study noted, there is a “limited accessibility of functional human brain tissue.”
Researchers at Stanford University School of Medicine developed a way to use human induced pluripotent stem cells (hiPSC) — which are able to generate almost any type of cell in the body — and direct them to mature (differentiate) into human neurons, astrocytes, and eventually into oligodendrocytes.
“We now have multiple cell types interacting in one single culture,” Sergiu Pasca, MD, an assistant professor of psychiatry and behavioral sciences and the study’s lead author, said in a Stanford news release written by Bruce Goldman.
The new system, Pasca added, “permits us to look close-up at how the main cellular players in the human brain are talking to each other.”
By week 26 of in-utero brain development of a baby, most neurons or nerve cells and astrocytes exist, and continue to mature in the following months.
Oligodendrocytes begin to appear much later. Those in the cerebral cortex, a brain region responsible for complex cognitive functions such as decision-making, scheduling, and foresight, begin populating the brain around the time of birth.
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