Using human skin cells, an international team including researchers from the Montreal Neurological Institute and Hospital of McGill University has created a method to generate microglia, a type of brain cell involved in preserving the function of neural networks and responding to injury and disease.
The method uses induced pluripotent stem (iPS) cells, which are blood or in this case skin cells that have been genetically reprogrammed to potentially become any other cell in the human body. The researchers guided these pluripotent cells to a new state by exposing the cells to a series of differentiation factors which mimicked the developmental origin of microglia. The resulting cells act very much like human microglial cells.
To verify that the former skin cells successfully transformed into copies of microglia, MNI postdoctoral fellow Luke Healy, working in the laboratory of Dr. Jack Antel, and first author Dr. Edsel Abud from the University of California, Irvine (UCI) compared them to brain material taken from human donors. They found that the iPS-microglia are virtually indistinguishable from human-derived microglia.
Previous research has shown that microglial cells interact with amyloid beta, an amino acid that builds up in the brains of Alzheimer’s patients. They also act as a switch for inflammatory response in the brain, and neuroinflammation is believed to be a factor in Alzheimer’s, although its exact role is unknown.
"Microglia play an important role in Alzheimer's and other diseases of the central nervous system,” said Mathew Blurton-Jones, an assistant professor at UCI and the study’s senior author. “Recent research has revealed that newly discovered Alzheimer's-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies."
Along those lines, the researchers examined the genetic and physical interactions between Alzheimer's disease pathology and iPS-microglia. They are now using these cells in three-dimensional brain models to understand how microglia interact with other brain cells and influence AD and the development of other neurological diseases.
“Chronic inflammation is now being recognised as playing an important role in traditionally ‘degenerative’ diseases such as Parkinson’s disease, AD and Huntington’s disease,” says Healy. “This is in addition to the well-established roles of these cells in the pathogenesis of more immune-mediated diseases such as multiple sclerosis. To be able to produce disease-specific microglia will not only help us understand the biology behind microglial involvement in these diseases, it will help us conduct high-throughput screening of drugs to modulate microglial function that is altered in these patients.”
This research was published on April 19, 2017 in the journal Neuron.