By Don C. Reed

Imagine cartoon warriors; make them very tough. Give each one a spear and a shield — They are called microglia (my-cro-glee-uh) and they live in your brain.

Well, okay, I exaggerated just a bit — microglia don’t have spears and shields — but they are definitely part of the Central Nervous System’s defenses. Listen to an expert, Dr. Matthew Mark Blurton-Jones, of UC Irvine:

“Microglia are specialized cells that play critical roles in …immune defense”… (1)

So far, so good, right?

Unfortunately, like shell-shocked soldiers who may become confused and run the wrong way on the battlefield, microglia may actually increase the severity of some neurological diseases, such as Alzheimer’s disease, stroke, Parkinson’s disease, traumatic brain injury and autism.

Some diseases attack the microglia, so it cannot do its job.

One disease with a huge name, “Adult-onset leukoencephalopathy (ALSP)…is the clearest example of a disorder that affects microglia, the immune cell of the brain.”

But if scientists increased healthy microglia, it might help to fight back against disease.

First, how could we make enough microglial cells to be useful?

A “glow in the dark” fluorescence helped the scientists separate the cells more rapidly and accurately, so they were able to turn one million cells into fifty million. (As the cell turns into microglia, it glows, making identification and counting much easier.)

“Our team…established a highly reproducible method to differentiate (stem cells) into microglia.”

What difference could that make? They might guide the activity of genes. For instance, one important gene called CD 33 “is thought to influence Alzheimer’s disease by the clearance of beta-amyloid, (removing plaques and tangles from the brain)…” (2)

Using mouse models…the team has been examining the role of CD 33 and several other Alzhieimer’s disease-associated genes in human microglial function to “study important questions about the genetics and causes of Alzheimer’s disease…”

Reducing the impact of Alzheimer’s alone would be an incredible gift to humanity.

But there’s more.

“Many independent labs have now replicated our approach to perform cutting-edge research on a variety of human diseases….” (3)

Our microglial methods are now being used by groups around the world to study many other neurological diseases including Parkinson’s Disease, Frontotemporal Dementia, Schizophrenia, and Autism.”

With continued CIRM support, Dr. Blurton-Jones’ group has also recently expanded their studies to examine the role of microglia in a devastating pediatric disease called Sanfilippo Syndrome. (4)

“ Our CIRM-funded research is … exploring whether we can generate and transplant healthy microglia into a mouse model of Sanfilippo Syndrome to … slow disease progression.”

1. https://www.cirm.ca.gov/print/our-progress/awards/transplantation-pluripotent-stem-cell-derived-microglia-treatment-adult-onset

2. https://www.cirm.ca.gov/our-progress/awards/optimizing-differentiation-and-expansion-microglial-progenitors-human

3. https://www.cirm.ca.gov/our-progress/awards/optimizing-differentiation-and-expansion-microglial-progenitors-human-pluripotent-stem-cells-study-and-treatment-neurological-disease/

4. https://www.cirm.ca.gov/our-progress/awards/transplantation-genetically-corrected-ipsc-microglia-treatment-sanfilippo-syndrome-mpsiiia/).

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