Daily trips to the local grocery store have become a thing of the past for many with the rise of wholesale stores like Costco and online giants like Amazon. Buying in bulk is attractive for people who lead busy lives, have large families, or just love having endless pairs of clean socks.
Scientists who study neurodegenerative diseases like Alzheimer’s and Parkinson’s use disease-in-a-dish models that are much like the daily visits to the nearby Safeway. They can make diseased brain cells, or neurons, from human pluripotent stem cells and study them in the lab. But often, they can’t generate large enough quantities of cells to do important experiments like test new drugs or develop diagnostic platforms to identify disease at an earlier age.
What scientists need is a Costco for brain cells, a source that can make diseased brain cells in bulk. Such a method would open a new avenue of research into what causes neurodegeneration and how the aging process affects its progression.
This week, this need was answered. A team of researchers from Lund University in Sweden developed a method that can efficiently generate neurons from patients with a range of neurodegenerative diseases including Parkinson’s, Huntington’s and Alzheimer’s disease. The study was published in EMBO Molecular Medicine and was led by senior author Dr. Malin Parmar.
Diseased neurons made by the Lund University team. (Photo, Kennet Ruona)
Parmar and her team took an alternative approach to making their neurons. Their technology involves converting human skin cells into neurons without reprogramming the skin cells back to a pluripotent stem cell state first. This process is called “direct conversion” and is considered an effective shortcut for generating mature cells like neurons in a dish. Direct conversion of skin cells into neurons was first published by Dr. Marius Wernig, a CIRM-grantee and professor at Stanford University.
There is also scientific evidence suggesting that reprogramming patient cells back to a pluripotent state wipes out the effects of aging in those cells and has a Benjamin Button-like effect on the resulting neurons. By directly converting patient skin cells into neurons, many of these aging “signatures” are retained and the resulting neurons are more representative of the aging brain.
So how did they make brain cells in bulk? Parmar explained their method in a Lund University news release,
“Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein’s impact in the cells during the conversion process, we’ve seen completely different results.”
Besides blocking REST, the team also turned on the production of two proteins, Ascl1 and Brn2, that are important for the development of neurons. This combination of activating pro-neural genes and silencing anti-neural genes was successful at converting skin cells into neurons on a large scale. Parmar further explained,
“We’ve been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy.”
As mentioned previously, this technology is valuable because it provides better brain disease models for scientists to study and to screen for new drugs that could treat or delay disease onset. Additionally, scientists can study the effects of the aging in the brain at different stages of neurodegeneration. Aging is a well-known risk factor for many neurodegenerative diseases, especially Alzheimer’s, so the ability to make large quantities of brain cells from elderly Alzheimer’s patients will unlock new clues into how age influences disease.
Co-author Dr. Johan Jakobsson concluded,
“This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on these cells to get closer to the diseases.”
For more on this study, check out this short video provided by Lund University.