Stem cell stories that caught our eye: relief for jaw pain, vitamins for iPSCs and Alzheimer’s insights

Jaw bone stem cells may offer relief for suffers of painful joint disorder
An estimated 10 million people in the US – mostly women –  suffer from problems with their temporomandibular joint (TMJ) which sits between the jaw bone and skull. TMJ disorders can lead to a number of symptoms such as intense pain in the jaw, face and head; difficulty swallowing and talking; and dizziness.

ds00355_im00012_mcdc7_tmj_jpgThe TMJ is made up of fibrocartilage which, when healthy, acts as a cushion to enable a person to move their jaw smoothly. But this cartilage doesn’t have the capacity to heal or regenerate so treatments including surgery and pain killers only mask the symptoms without fixing the underlying damage of the joint.

Reporting this week in Nature Communications, researchers at Columbia University’s College of Dental Medicine identified stem cells within the TMJ that can form cartilage and bone – in cell culture studies as well as in animals. The research team further showed that the signaling activity of a protein called Wnt leads to a reduction of these fibrocartilage stem cells (FSCSs) in animals and as a result causes deterioration of cartilage. But injecting a known inhibitor of Wnt into the animals’ damaged TMJ spurred growth and healing of the joint.

The team is now in search of other Wnt inhibitors that could be used in a clinical setting. In a university press release, Jeremy Mao, a co-author on the paper, talked about the implications of these results:

“They suggest that molecular signals that govern stem cells may have therapeutic applications for cartilage and bone regeneration. Cartilage and certain bone defects are notoriously difficult to heal.”

Take your vitamins: good advice for people and iPS cells
From a young age, we’re repeatedly told how getting enough vitamins each day is important for a healthy life. Our bodies don’t produce these naturally occurring chemicals but they carry out critical biochemical activities to keep our cells and organs functioning properly.

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Carrots: a great source of vitamin A. Image source: Wikimedia Commons

Well, it turns out that vitamins are also an important ingredient in stem cell research labs. Results published the Proceedings of the National Academy of Sciences (PNAS) this week by scientists in the UK and New Zealand show that vitamin A and C work together synergistically to improve the efficiency of reprogramming adult cells, like skin or blood, into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs).

By the time a stem cell has specialized into, let’s say, a skin cell, only skin cell-specific genes are active while others genes, like those needed for liver function, are shut down. Those non-skin genes are silenced through the attachment of chemical tags on the DNA, a process called methylation. It essentially provides the DNA with the means of maintaining a skin cell “memory”. To convert a skin cell back into a stem cell-like state, researchers in the lab must erase this “memory” by adding factors which demethylate, or remove the methylation tags on the silenced, non-skin related genes.

In the current research picked up by Science Daily, the researchers found that both vitamin A and C increase demethylation but in different ways. The study showed that vitamin A acts to increase the production of proteins that are important for demethylation while vitamin C acts to enhance the enzymatic activity of demethylation.

These insights may help add to the growing knowledge on how to most efficiently reprogram adult cells into iPSCs. And they may prove useful for a better understanding of certain cancers which contain cells that are essentially reprogrammed into a stem cell-like state.

New angles for dealing with the tangles in the Alzheimer’s brain
The memory loss and overall degradation of brain function seen in people with Alzheimer’s Disease (AD) is thought to be caused by the accumulation of amyloid and tau proteins which form plaques and tangles in the brain. These abnormal structures are toxic to brain cells and ultimately lead to cell death.

But other studies of post-mortem AD brains suggest a malfunction in endocytosis – a process of taking up and transporting proteins to different parts of the cell – may also play a role. While follow up studies corroborated this initial observation, they didn’t look at endocytosis in nerve cells so it remained unclear how much of a role it played in AD.

In a CIRM-funded study published this week in Cell Reports, UC San Diego researchers made nerve cells from human iPSCs and used the popular CRISPR and TALEN gene editing techniques to generate mutations seen in inherited forms of AD. One of those inherited mutations is in the PS1 gene which has been shown to play a role in transporting amyloid proteins in nerve cells. The research confirmed that this mutation as well as a mutation in the amyloid precursor protein (APP) led to a breakdown in the proper trafficking of APP within the mutated nerve cells. In fact, they found an accumulation of APP in a wrong area of the nerve cell. However, blocking the action of a protein called secretase that normally processes the APP protein helped restore proper protein transport. In a university press release, team leader Larry Goldstein, explained the importance of these findings:

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Larry Goldstein.
Image: UCSD

“Our results further illuminate the complex processes involved in the degradation and decline of neurons, which is, of course, the essential characteristic and cause of AD. But beyond that, they point to a new target and therapy for a condition that currently has no proven treatment or cure.”

 

 

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