Stem Cell Stories That Caught our Eye: Insights into a healthy brain, targeting mutant cancers and commercializing cell therapies

Here’s your weekly roundup of interesting stem cell stories!

Partnership for a healthy brain. To differentiate or not to differentiate. That is the question the stem cells in our tissues and organs face.

In the case of the brain, neural precursor cells can either remain in a stem cell state or they can differentiate into mature brain cells called neurons and astrocytes. Scientists are interested in understanding how the brain maintains the balance between these different cell states in order to understand how disruption to this balance are associated with psychiatric and neurodegenerative diseases.

Scientists from the Salk Institute, led by Genetics Professor Rusty Gage, published a study this week in Cell Stem Cell that sheds light on how this imbalance can cause brain disease. They found that a partnership between two proteins determines whether a neural precursor develops into a neuron or an astrocyte.

One of these proteins is called Nup153. It’s a protein that’s part of the nuclear pore complex, which sits on the surface of the nuclear membrane and controls the entry and exit of various proteins and molecules. In collaboration with another Salk team under the leadership of Martin Hetzer, Gage discovered that Nup153 was expressed at different levels depending on the cell type. Neural precursors had high levels of Nup153 protein, immature neurons had what they defined as an intermediate level while astrocytes had the lowest level.

When they blocked the function of Nup153, neural precursors differentiated, which led them to conclude that the levels of Nup153 can influence the fate of neural precursor cells. The teams also discovered that Nup153 interacts with the transcription factor Sox2 and that the levels of Sox2 in the different cell types was similar to the levels of Nup153.

A fluorescent microscopy image shows Nup153 (red) in pore complexes encircling and associating with Sox2 (green) in a precursor cell nucleus. Credit: Salk Institute/Waitt Center

In a Salk News release, first author on the study, Tomohisa Toda, explained how their findings shed light on basic cellular processes:

“The fact that we were able to connect transcription factors, which are mobile switches, to the pore complex, which is a very stable structure, offers a clue as to how cells maintain their identity through regulated gene expression.”

Gage’s team will next study how this partnership between the nuclear pore complex and transcription factors can influence the function of neurons in hopes of gaining more understanding of how an imbalance in these interactions can lead to neurological diseases.

“Increasingly, we are learning that diseases like schizophrenia, depression and Alzheimer’s all have a cellular basis. So we are eager to understand how specific brain cells develop, what keeps them healthy and why advancing age or other factors can lead to disease.”

Tomohisa Toda and Rusty Gage. Credit: Salk Institute

Targeting KRAS Mutant Cancer.

CIRM-funded scientists at UC San Diego School of Medicine have developed a new strategy to target cancers that are caused by a mutation in the KRAS gene. Their findings were published in the journal Cancer Discovery.

The KRAS protein is essential for normal signaling processes in tissues, but mutant versions of this protein can cause cancer. According to a UC San Diego Health news release about the study, “there are currently no effective treatments for the 95 percent of pancreatic cancers and up to 30 percent of non-small cell lung cancers with KRAS mutations.”

To address this need, the team identified a biomarker called αvb3 that is associated with cancers dependent on the KRAS mutation. They observed that a protein called Galectin-3 binds to αvb3, which is an integrin receptor on the surface of cancer cells, to promote mutant KRAS’s cancer-causing ability.

This realization offered the team a path towards potential treatments. By inhibiting Galectin-3 with a drug called GCS-100, the scientists would make KRAS-addicted cancers go cold turkey. Senior author on the study, David Cheresh, explained,

“This may be among the first approaches to successfully target KRAS mutant cancers. Previously, we didn’t understand why only certain KRAS-initiated cancers would remain addicted to the mutation. Now we understand that expression of integrin αvb3 creates the addiction to KRAS. And it’s those addicted cancers that we feel will be most susceptible to targeting this pathway using Galectin-3 inhibitors.”

Cheresh concluded that this novel approach could pave the way for a personalized medicine approach for KRAS-addicted cancers.

“KRAS mutations impact a large number of patients with cancer. If a patient has a KRAS mutant cancer, and the cancer is also positive for αvb3, then the patient could be a candidate for a therapeutic that targets this pathway. Our work suggests a personalized medicine approach to identify and exploit KRAS addicted tumors, providing a new opportunity to halt the progression of tumors that currently have no viable targeted therapeutic options.”

Commercializing cell therapy.

Our friends at RegMedNet made an infographic that illustrates how cell therapies have developed over time and how these therapies are advancing towards commercialization.

The infographic states, “The cell therapy industry is rapidly evolving, with new techniques, technology and applications being developed all the time. After some high-profile failures, all eyes are on regulating existing therapies to ensure patient safety is paramount. Legislators, regulators and other stakeholders around the world are navigating a difficult line between hope, hype and the scientific evidence.”

Check out their timeline below and visit the RegMedNet website for more news and information about the regenerative medicine field.

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