Tag: liver disease

Categories : Immune System Medical Research & Technology New Compounds and TreatmentsTags :

New Treatment may Regenerate Liver Scarring

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Japanese researchers have come up with a new approach that could revolutionise the treatment and prevention of liver disease damage and possibly regenerate liver scarring.

This novel strategy involves small extracellular vesicles (sEVs), which are lipid-enclosed particles that are naturally released from a cell. The ones used in this study derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs).

Cirrhosis (scarring of the liver) and other chronic liver diseases result in up to 2 million deaths reported annually around the world, these in turn account for approximately 3.5% of annual deaths globally. As the only treatment for clinically advanced cirrhosis liver transplantation, targeted therapies for modulating fibrosis and aiding tissue regeneration.  The ability to control fibrosis–the growth of fibrous tissue in response to damage– is often lost in livers under advanced cirrhosis.  The research builds upon this.

One of the most popular approaches is cell therapy, where mesenchymal stromal cells (MSCs) and macrophages have shown the potential to reduce liver fibrosis. MSCs are able to transform into a number of different cells. They are cost-effective, being available not only from bone marrow, but also from medical waste such as umbilical cord tissue, adipose (fatty) tissue, and dental pulp.

Apart from the ease of availability, MSCs can also be lab-grown. MSCs don’t replace tissue but instead have been shown to be medical signaling cells that indirectly produce cytokines, chemokines, growth factors, and exosomes that are crucial for repairing and regenerating damaged tissue.

Previous research showed that MSCs have anti-inflammatory, anti-fibrotic, and anti-oxidative effects through these humoural factors. MSCs also have lower potential for provoking an immune response and therefore rejection, enabling their use in both within the same individual and another.

In a series of experimental mice studies, researchers pre-conditioned fat extracellular vesicles with interferon gamma (IFN-γ), an important immune system signaller. They showed that this increases the number of anti-inflammatory macrophages, which are the key players in tissue repair, reducing fibrosis and promoting tissue regeneration.

They reported that both MSCs derived from fatty tissue (AD-MSC-sEVs) and AD-MSC-γ-sEVs can boost macrophage motility and phagocytic activity. In addition, they also show that AD-MSC-γ- sEVs can effectively control inflammation and fibrosis in mice with cirrhosis.

They found thatAD-MSC-derived sEVs can affect the shape and function of macrophages, effectively recruiting them into damaged areas to initiate tissue repair.

In an interview, researcher Dr Atsunori Tsuchiya at Niigata University, explained that, “Both mesenchymal stromal cells and macrophages are reported to have therapeutic effects for liver cirrhosis, however relationship of both cells and mechanisms of action was not clear. We challenged this problem.”

He continued, “We found the important fact that extracellular vesicles from interferon-γ can induce the tissue repair macrophages, which can regress fibrosis and promote liver regeneration effectively.” 

Dr Suguru Takeuchi, another of the researchers at Niigata University, concurred: “In our previous study, we reported that intravenous administration of mesenchymal stromal cells migrated to the lung, can work as ‘conducting cells’ and affect to macrophages ‘working cells’ in the liver.

“In this study we first elucidated that extracellular vesicles from mesenchymal stromal cells are key molecules to affect the macrophages.”

This study, which complements macrophage therapy, holds potential as a strategy for treating liver diseases using small extracellular vesicles pre-conditioned with IFN-γ. However, further development is needed, as well as uncovering the mechanisms by which they increase Treg cell count.

“Our results showed that modified extracellular vesicles can become a new therapeutic strategy for liver cirrhosis,” said Professor Shuji Terai, Niigata University.

Source: News-Medical.Net

Journal information: Takeuchi, S., et al. (2021) Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. npj Regenerative Medicine. oi.org/10.1038/s41536-021-00132-4.

Categories : Gender Substance UseTags :

Alcoholic Liver Disease Is ‘Astronomical’ in Young Women

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Image by ds_30 from Pixabay

Rates of alcoholic liver disease are skyrocketing in young women, doctors in the US have warned. Much of it has to do with added pressures on women in the pandemic.

Alcoholic liver disease — including milder fatty liver and the permanent scarring of cirrhosis, as well as alcoholic hepatitis — are up 30% over the last year at the University of Michigan’s health system, said Dr Jessica Mellinger, a liver specialist there. Severe liver disease and cirrhosis can see survival rates as low as 10%.

The route by which liver disease develops varies according to the individual, although obesity, genetics and underlying health conditions play a role. Moderate consumption of alcohol, a glass or two of wine daily, is unlikely to contribute to it.

However, Dr Mellinger says that along with her colleagues, she has seen alcohol consumption edging upward, to a bottle of wine per day which results in increased risk of serious liver disease.

Since the beginning of the pandemic, no data on overall increases in serious alcoholic liver disease has yet been compiled by The Centers for Disease Control and Prevention. But, Dr Mellinger said, “in my conversations with my colleagues at other institutions, everybody is saying the same thing: ‘Yep, it’s astronomical. It’s just gone off the charts.’ “

The age demographic is also changing. “We’re seeing kids in their late 20s and early 30s with a disease that we previously thought was kind of exclusive to middle age,” she said.

The pressures of the COVID pandemic are partly to blame, and in many cases the extra burden is falling on women – who are already more susceptible to alcohol because they have a smaller water volume to distribute alcohol into and their bodies do less ‘first pass’ metabolism of alcohol in the stomach. Popular culture and advertising also encourages women to drink.

Psychological factors such as eating disorders and trauma from sexual abuse also fuel the disease.

“Whether this is early life sexual trauma or they are in a recent or ongoing abusive relationship, we see this link very, very closely,” said psychiatrist Dr Scott Winder, a clinical associate professor at the University of Michigan who treats liver disease patients. “Just the sheer amount of trauma is really, really tragic.”

The lack of overlap between the various fields in this complex relationship results in what he calls a “tragic gap”.

“The cultures of hepatology and the cultures of psychology and psychiatry are very disparate; we see patients very differently,” so physicians aren’t coordinating care, even when they should, he said.

Advanced liver disease may leave no other recourse than a liver transplant.
“Unfortunately, transplantation is finite,” said Dr Haripriya Maddur, a hepatologist at Northwestern University. “There aren’t enough organs to go around. What it unfortunately means is that many of these young people may not survive, and die very young — in their 20s and 30s. It’s horrific.”

Some people such as Jessica Duena, a teacher who was diagnosed with alcoholic hepatitis at 34, and was hospitalised several times following the death of her boyfriend from heroin, have managed to turn the disease around and are encouraging others to do the same. 

She wrote about her long-held secret in the Louisville Courier-Journal: “I’m Jessica, I’m the 2019 Kentucky State Teacher of the Year, I’m an alcoholic and I’ve been suffering in silence for years.”

She received hundreds of responses, mostly women like herself who were in similar circumstances.

“What I’ve noticed is quite a few of the women, typically, they were either educators, they were moms or they happened to be nurses or attorneys,” Duenas said. They poured their hearts out about the crushing and constant stress of kids, work and home life.

They also complained of the pressures outside the home. “Imagine being a teacher who gets evaluated on how your students do, given the situation today,” Duenas says. “I mean, that makes me want to drink for them, you know — like that’s a terrible pressure to be under.”

Duenas has started writing about the stories of such people who reach out to her on her website, www.bottomlesstosober.com.

Source: NPR