iPSC-derived microglia may help advance ALS research, therapies

Ncyte Microglia exhibit key characteristics of the brain immune cell

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Ncardia has launched a stem cell-derived model of human microglia to advance research into neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), where these cells play an important role.

Microglia, the resident immune cells in the brain, help support the function of nerve cells, but if they become overly active, they can contribute to the development and progression of neurodegenerative conditions, including ALS.

Called Ncyte Microglia, the new product contains microglia that closely resemble the primary microglia in the human brain. They exhibit key characteristics, including phagocytosis — the cells’ ability to ingest and eliminate microorganisms and damaged cells — the production of specific microglial markers, and the production of inflammatory molecules called cytokines in response to a threat.

“The introduction of Ncyte Microglia is a significant step forward in providing human-relevant models for [central nervous system] research,” Jeroen de Groot, divisional CEO of Ncardia, said in a company press release. “By offering researchers reliable, scalable, and functionally relevant microglia, we aim to accelerate the discovery of novel therapies for devastating neurological diseases.”

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What will Ncyte Microglia do in ALS?

ALS is caused by the progressive dysfunction and death of motor neurons — the nerve cells that control voluntary movements — leading to muscle weakness. What leads to the loss of these neurons isn’t completely understood, but inflammation is thought to contribute to the disease’s onset and progression. This inflammation is driven in part by the excessive activation of microglia.

Ncyte Microglia contains microglia derived from induced pluripotent stem cells (iPSCs). These are created from skin or blood cells of healthy donors or patients and are reprogrammed into lab-made stem cells that can differentiate into almost any human cell type. iPSCs are then given specific chemical or biological cues that allow them to differentiate into microglia.

The final cells have several important characteristics of microglia, including their markers and ramified shape, and can be used to better study the behaviors and interactions of microglia that might contribute to disease progression. They may also be used to evaluate therapeutic compounds targeting inflammation, according to Ncardia. The cells are preserved in a frozen state, but become fully functional once they thaw and grow in the lab.

In addition to microglia, the company also provides ready-to-use, cell-based assays for ALS that use iPSC-derived motor neurons. These assays can be used to screen treatment candidates for ALS.