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Liver and seven tiny organs regrown from stem cells (2015-07-23)

Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory. It is the first time researchers have restored function to a severely damaged liver in a living animal using stem cells.

It’s just one example of scientists growing tiny versions of organs in animals and in the lab to study development and disease, and test potential treatments. Many of these organs also represent the first steps towards growing whole organs – or parts of organs – for transplant.


IMAGE - Transplanted hepatic progenitor cells can self-renew (yellow) and differentiate into hepatocytes (green) to repair the damaged liver (Image: Wei-Yu Lu, MRC Centre for Regenerative Medicine, The University of Edinburgh’)

Researchers from the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh transplanted liver stem cells into mice with liver failure. They found that over several months major areas of the liver were regrown from these cells, improving the structure and function of their livers.

The liver has a great capacity to repair itself, however in conditions such as cirrhosis and acute liver failure, it becomes damaged beyond repair.

Within the liver, hepatocytes are the essential cells that make many proteins and break down toxins, and while they have been used for transplantation their use has been limited as they don’t grow well under laboratory conditions. Liver stem cells overcome this as they can be grown under laboratory conditions and have the flexibility to change into hepatocytes or other important types of liver cells.

This is the first time that researchers have proven that liver stem cells can regrow the liver to such an extent. If they can show the same effect with human cells then they may be useful as a treatment for liver failure. Transplanting such cells into patients with liver failure could one-day offer an alternative to liver transplants.

In the long term, scientists hope to find a way of stimulating the patient’s own stem cells to repair the damaged liver using medicines.

The research was funded by the Medical Research Council, the UK Regenerative Medicine Platformopens in new window and the Wellcome Trustopens in new window. It is published in the journal Nature Cell Biology.

Small organs, or parts of them, are useful for studying both development and disease, and for toxicity testing or testing new treatments. In some cases, mini organs will be able to replace research using animals.

But they also offer a tantalising glimpse of a world in which we can grow complex solid organs for transplant. These tiny organs – often more like proto-organs with just some of an organ’s functions – are quite literally ‘starting small’, first seeing if it’s even possible.

Here we list seven tiny organs that have been grown so far.

Itty-bitty intestines

In a study at the Cincinnati Children’s Hospital Medical Center, researchers used induced pluripotent stem cells to grow human intestinal tissue in the lab. They then connected the tissue to the kidney of a mouse, providing it with a blood supply to allow it to mature into a piece of human intestine. This technique could provide a useful way of studying and ultimately treating gastrointestinal diseases in the future.

Compact kidneys

Working lab-grown kidneys have been transplanted into rats by researchers from the Center for Regenerative Medicine in the US. The team stripped down a rat kidney to a scaffold-like structure, before introducing rat kidney and blood vessel cells that grew into a new functioning kidney. They then transplanted the organ into rats where it successfully filtered blood and produced urine.

Small skin

An MRC-funded team led by King’s College London and the San Francisco Veteran Affairs Medical Center has grown a 3D piece of skin in the lab. Using induced pluripotent stem cells, they produced an unlimited supply of skin cells, some of which were then used to grow a small piece of skin. The lab-grown skin has a working natural barrier that protects it from losing moisture, and prevents it from absorbing chemicals and toxins. This makes it particularly useful for studying a range of skin conditions, and for testing drugs and cosmetics.

Tiny thymi

The thymus is an immune system organ which sits just in front the heart. Another group of researchers at the MRC Centre for Regenerative Medicine have reprogrammed mouse cells called fibroblasts, which normally become connective tissue, to instead become thymus cells. When mixed with other thymus cell types and transplanted into mice, the cells grew into a functioning mouse thymus.

Teeny tickers

Miniature human hearts have been grown in the lab using a mouse heart ‘scaffold’. Researchers from the University of Pittsburgh removed all the cells from a mouse heart, leaving a skeleton-like structure, before reintroducing immature human heart cells. After just a few weeks the cells developed into beating heart tissue.

Small-scale stomachs

Three-dimensional human gastric tissue has been grown by a team at the Cincinnati Children’s Hospital Medical Center using human pluripotent stem cells that were coaxed into becoming stomach cells. The structures are only three millimetres in diameter, but could turn out to be useful disease models for understanding how the stomach develops and is affected by different diseases. Plans are already underway to use these tiny organs for studying how the bacterium, H. pylori, causes stomach ulcers and gastric disease.

It’s worth mentioning that while we’re talking about tiny organs, Prof Martin Birchall at University College London has successfully transplanted stem cell-based tracheas and larynxes into patients. link...

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