Liver Regeneration: ‘Switch’ Changes Cells Back

Liver Regeneration: ‘Switch’ Changes Cells Back

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Harvard Stem Cell Institute scientists at Boston Children’s Hospital have new evidence in mice that it may be possible to repair a chronically diseased liver by forcing mature liver cells to revert back to a stem cell-like state.

The researchers, led by Fernando Camargo, PhD, happened upon this discovery while investigating whether a biochemical cascade called Hippo, which controls how big the liver grows, also affects cell fate. The unexpected answer, published in the journal Cell, is that switching off the Hippo-signaling pathway in mature liver cells generates very high rates of dedifferentiation. This means the cells turn back the clock to become stem-cell like again, thus allowing them to give rise to functional progenitor cells that can regenerate a diseased liver.

The liver has been a model of regeneration for decades, and it’s well known that mature liver cells can duplicate in response to injury. Even if three-quarters of a liver is surgically removed, duplication alone could return the organ to its normal functioning mass. This new research indicates that there is a second mode of regeneration that may be repairing less radical, but more constant liver damage, and chips away at a long-held theory that there’s a pool of stem cells in the liver waiting to be activated.

“I think this study highlights the tremendous plasticity of mature liver cells,” said Camargo, who is an associate professor in the Harvard Department of Stem Cell and Regenerative Biology, and based in the Stem Cell Program at Boston Children’s Hospital. “It’s not that you have a very small population of cells that can be recruited to an injury; almost 80 percent of hepatocytes [liver cells] can undergo this cell fate change.”

Much of the work dissecting the biology of these changes and establishing that the dedifferentated cells are functional progenitors was carried out by the Cell paper’s first co-authors Dean Yimlamai, MD, PhD, and Constantina Christodoulou, PhD, of Boston Children’s Hospital.

The next step, Camargo said, would be to figure out how Hippo’s activity changes in cells affected by chronic liver injury or diseases such as hepatitis. In the long term, this work could lead to drugs that manipulate the Hippo activity of mature liver cells inside of patients to spur dedifferentiation and hasten healing.

It might also be possible to control Hippo signaling to grow countless liver progenitor cells in a laboratory dish for transplant, which Camargo’s team pursued in the Cell paper using mice born with a genetic liver disease. They cultured healthy liver progenitor cells and transplanted them into the diseased mice. Over a period of three or four months, the transplanted liver cells engrafted and the animals saw improvement of their condition.

“People have been trying to use liver cell transplants for metabolic diseases since the early 90s, but because of the source of cells—discarded livers—they were unsuccessful,” Camargo said. “With this unlimited source of cells from a patient, we think that perhaps it’s time to think again about doing hepatocyte or progenitor cell transplants in the context of liver genetic disorders.”

The observation that mature liver cells dedifferentiate comes after a number of related studies published in the past year from Harvard researchers showing that mature cells in several different internal organs, including the kidneys, adrenal glands, and lungs, are more plastic than we once assumed.

“I think that maybe it is something that people have overlooked because the field has been so stem cell centric,” said Camargo, also a Harvard Stem Cell Institute Principal Faculty member. “But I think the bottom line is that the cells that we have in our body are plastic, and understanding pathways that underlie that plasticity could be another way of potentially manipulating regeneration or expanding some kind of cell type for regenerative medicine.”

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The above story is based on materials provided by Harvard UniversityNote: Materials may be edited for content and length.

4 Simple Steps to Detoxifying Your Gut After the Holidays

4 Simple Steps to Detoxifying Your Gut After the Holidays

by Elizabeth Renter,
Many people use the holiday season to indulge in foods they wouldn’t normally eat. Even those who ascribe to a natural diet may find themselves crossing lines they wouldn’t typically cross when encountered with foods from their childhood or old favorites while among family and friends. Indulging during the holidays is OK! Don’t feel bad! But remember to get back on track. Here are 4 solutions that might help.

1. Water

First off, get to hydrating. Flushing the remnants of the holiday foods out begins with the most natural consumable substance out there—water. The effectiveness of each of your body’s systems (digestive, circulatory, etc.) depends on proper hydration. And many foods we associate with the holidays can actually dehydrate us. Up your water intake and eat foods with high water contents (fruits and vegetables) to help get your hydration back to proper levels. Of course it is preferable to filter your water through a high quality water filtration system.

2. Garlic

In addition to staying hydrated, you need to rebalance your gut bacteria. There are many foods out there to avoid and consume to promote a healthy gut, but just one of those foods is garlic. Garlic is a powerful food and, when raw, can be extremely effect in solving your health woes. Chewing a piece of raw garlic releases its effective enzymes. Once in the digestive system, these enzymes work to eliminate destructive gut bacteria while keeping the “good bacteria” alive. In some studies, garlic has been found to be even more effective than penicillin, and without annihilating the millions of good bacteria in your gut.

If raw garlic doesn’t sound appetizing, try making it more palatable with honey. Peel and separate garlic cloves. Cover with local, raw honey in a mason jar and allow to sit for a few weeks. The health benefits of honey and garlic are astounding, but this garlic-honey combo is a great cure-all, effective for treating colds, preventing infection, and of course, detoxifying the gut.

3. Apples

Add apples to your diet. Apples contain a flavonoid called Phlorizidin which helps regulate the production of bile in the liver. Bile assists the liver in removing toxins from the body. In addition, apples are an excellent source of fiber which can help flush the intestines.

4. Exercise

Exercise is another important, and often overlooked, aspect of detoxing. In an active body, every internal system works more efficiently. An inactive body is sort of like a car sitting on blocks—the gas doesn’t get used and the parts begin to get rusty and stiff. When the car is maintained and used regularly, it goes through a steady diet of fuel and uses that fuel more efficiently. Also, working up a sweat can help rid the body of toxins through the skin. Try a brisk walk in the sunshine to boost vitamin D production (another important detox component).

Detoxing after the holidays doesn’t have to be difficult. Just pick up where you left off—with healthy practices—and your body will rebound accordingly.
Read more: Natural Society 

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