Stem cells responsible for repairing the womb following menstruation can also promote endometriosis and endometrial cancer if they become dysfunctional, researchers have found.

Such malfunctioning stem cells also can reduce the chances of success for women undergoing in vitro fertilization (IVF), the study shows.

The researchers’ findings were reported in “Endometrial Axin2+ Cells Drive Epithelial Homeostasis, Regeneration, and Cancer following Oncogenic Transformation,” a study published in the journal Cell Stem Cell.

Using a technique called in vivo lineage tracing in female mice, investigators from the Hunter Medical Research Institute in Australia and their colleagues discovered that stem cells located at the base of special glands found throughout the inner lining of the womb (endometrium) are responsible for replenishing the endometrial tissue that is lost during menstruation.

In vivo lineage tracing is a technique that allows scientists to label and follow specific cells inside an organism. In so doing, the team discovered these stem cells contained high levels of a gene called Axin 2, which has been found to be active in cell types from other highly regenerative tissues.

When the researchers specifically destroyed Axin 2-positive stem cells in the wombs of female mice, they found the endometrium was no longer able to repair itself and became highly dysfunctional. Moreover, when investigators introduced cancer-associated mutations into these stem cells, the cells started to malfunction and to fuel the development of endometrial cancer.

“What we are able to show is that if you cause mutations in these cells, you get endometrial cancer,” Pradeep Tanwar, PhD, lead researcher and senior author of the study, said in a news story.

“What we now hypothesise is that when women have endometriosis, what they have is an expansion of these mutated cells. These cells end up going into the abdominal cavity. Because they are so highly regenerative — because these are the cells that are repairing the uterus in each cycle — they start making uterine-like tissues in the abdominal cavity — which is what endometriosis is,” said Tanwar, also an associate professor at the Hunter Medical Research Institute.

Tanwar also believes the malfunction of these stem cells could be the reason why women undergoing fertility treatments fail to conceive.

“Some women have repeated failed IVF cycles because their endometrium is too thin, and the embryos cannot implant,” he said. “We now know that these cells in these women are going to be defective, and that is why the repair is not happening properly,” he said.

The Hunter researchers spent seven years “exhaustively testing” their findings, Tanwar said. He said they collected and banked gynecological tissue samples from hundreds of women treated at the center.

Given the wide implications of these findings, many scientists around the globe have reached out to congratulate the team on their discovery, he said.

“There have been so many questions about these conditions, and this has given us a framework to start addressing those, and — hopefully — come up with some answers,” Tanwar said.

“There is huge potential in the study, and there is huge potential in what we are doing. This cell is affecting many of these gynaecological diseases, which are mainly uterine based,” he added.

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Research led by the University of California, Los Angeles (UCLA) has uncovered a new process that may help explain how Type 2 diabetes develops. In tests on live mice and human cells in the lab, the team found a new mechanism besides insulin resistance and high glucose levels that triggers pancreatic cells to begin overproducing insulin.

Type 2 diabetes is the form of the disease that’s usually a result of lifestyle choices, such as poor diet and not enough exercise. It involves a kind of vicious cycle of insulin – beta cells in the pancreas produce too much insulin, which causes the body to become resistant to it. That in turn means the beta cells could produce even more to compensate.

It was long thought that high glucose levels – most commonly caused by eating too much sugary and fatty foods – was the trigger for the beta cells to begin overproducing insulin. But it’s also been shown in the past that even beta cells isolated in a lab dish can over-secrete insulin, without glucose playing a part.

So the team on the new study investigated what else could be causing beta cells to overproduce insulin. In tests on obese, pre-diabetic mice, the researchers discovered a new, separate molecular pathway that can induce insulin secretion without glucose. Instead, the trigger appears to be fatty acids.

When levels of these fatty acids rose too high in the mice, a protein called Cyclophilin D (CypD) caused protons to “leak” into the mitochondria of the beta cells. This triggers them to boost production of insulin.

To check the mechanism, the team then engineered mice without the gene that codes for CypD, and found that their insulin stayed at regular levels.

The researchers also investigated whether the same mechanism could be occurring in humans, by testing human pancreas cells isolated in the lab. When exposed to high levels of fatty acids – levels found in obese humans – the cells began to produce more insulin. Again, there was no glucose present.

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Several major strides have been made towards a cure for HIV in recent years, and now, researchers from the University of California San Diego (UCSD) may have found a new potential target. In lab tests, the team identified a cellular “switch” that could be turned off to clear out the virus lying dormant inside cells.

Currently, people with HIV undergo a life-long treatment called antiretroviral therapy, which suppresses symptoms and keeps the infection from developing into AIDS. But it isn’t a full cure – the virus can lay dormant inside a patient’s cells, ready to start multiplying again if the treatment is ever stopped.

Finding ways to kill the virus while it lays dormant is the holy grail of HIV research, and now the UCSD team says it’s a step closer to a cure. They found that a particular RNA molecule appears to be elevated in people with HIV, and in tests on cultured cells they showed that silencing or removing it prevented HIV from recurring after antiretroviral therapy was stopped.

The molecule is what’s known as a long non-coding RNA (lncRNA), meaning it doesn’t encode for proteins but instead helps control the switching of genes on and off within a cell. The team has dubbed this particular molecule HIV-1 Enhanced LncRNA (HEAL). Interestingly, the HEAL gene appears to have emerged fairly recently, and it regulates HIV replication in immune cells.

“This is one of the key switches that the HIV field has been searching for three decades to find,” says Tariq Rana, an author of the study. “The most exciting part of this discovery has not been seen before. By genetically modifying a long noncoding RNA, we prevent HIV recurrence in T cells and microglia upon cessation of antiretroviral treatment, suggesting that we have a potential therapeutic target to eradicate HIV and AIDS.”

In experiments on isolated human immune cells in the lab, the researchers either silenced HEAL, or snipped it out of the genome using the gene-editing tool CRISPR-Cas9. In both cases, HIV didn’t re-emerge after the antiretroviral therapy stopped.

“Our results suggest that HEAL plays a critical role in HIV pathogenesis,” says Rana. “Further studies are needed to explain the mechanism that leads to HEAL expression after an individual is infected by HIV, but this finding could be exploited as a therapeutic target.”

Of course, this is a very early test, and it hasn’t yet been performed in animals, let alone humans. Still, it’s an interesting new avenue for research into a potential cure.

And it’s not the only one scientists are investigating. Earlier this year a team used a new type of antiretroviral therapy called LASER ART to suppress the virus, then snipped it out using CRISPR – effectively curing the infection in mice. Another team used stem cells to put a man into long-term remission for only the second time ever – but the treatment itself was dangerous, painful and not likely to be recommended to general patients in its current form.

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