Tuesday, 1 September 2015

A new era in medicine

In July of this year researchers at the Medical Research Council (MRC) Centre for Regenerative Medicine announced that they have regrown damaged livers in mice. 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. Why might you want to grow a tiny organ? 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 and this will undoubtedly sit well with activists who have long campaigned against animal testing for medical research purposes.

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 is a list of eight tiny organs that have been grown so far.

Little livers
Transplanted liver cells: 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’)
The MRC Centre for Regenerative Medicine researchers used liver stem cells, called hepatic progenitor cells, to regrow damaged livers in mice. After extracting the stem cells from healthy adult mice and maturing them in the lab, the researchers transplanted the cells into mice with liver failure.

In three months the cells had grown enough to partly restore the structure and function of the animals’ livers, providing hope that this technique could one day replace the need for liver transplants in humans. [1]

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. [3]

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. [4]

Small skin
Thymus cells (dark blue) against a background 
of kidney cells (pink) (Image: MRC Centre for 
Regenerative Medicine, the University of Edinburgh)

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. [5]

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. [2]

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 [6].

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. [7]

Bijou brains
A cross-section of a cerebral organoid
(Image copyright: IMBA/ Madeline A. Lancaster)
A team of scientists from the Institute of Molecular Biotechnology in Austria, in collaboration with scientists at the MRC Human Genetics Unit at the University of Edinburgh, has grown miniature brain-like ‘organoids’ with distinct brain regions, including a cerebral cortex and retina.

The team used human embryonic and human induced pluripotent stem cells that were provided with the oxygen and nutrients needed to mature into brain organoids. No one’s going to be growing brains – or even parts of brains for transplant – but the work will help us to understand the brain and any diseases and disorders that affect it: already, the team has grown organoids with a disorder called microcephaly. [8]

And finally…
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. What this will herald for patient care in the future remains to be seen. After all, there is already an inequality in healthcare here in the UK, sometimes dictated by a postcode lottery not to mention the debate of private versus public healthcare provision. The clinical judgements that are going to be required in order to make available these treatment options is going to come under even more scrutiny especially as it promises to mark a new era in medicine.

  1. Hepatic progenitor cells of biliary origin with liver repopulation capacity Nature Cell Biology (2015) doi:10.1038/nbt.3275
  2. An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts Nature Cell Biology (2014) doi:10.1038/ncb3023
  3. An in vivo model of human small intestine using pluripotent stem cells Nature Medicine (2014) doi:10.1038/nm.3737
  4. Regeneration and experimental orthotopic transplantation of a bioengineered kidney Nature Medicine (2013) doi:10.1038/nm.3154
  5. 3D in vitro model of a functional epidermal permeability barrier from human embryonic stem cells and induced pluripotent stem cells Stem Cell Reports (2014) doi:10.1016/j.stemcr.2014.03.009
  6. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells Nature Communications (2013) doi:10.1038/ncomms3307
  7. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids Nature (2014) doi:10.1038/nature13863
  8. Cerebral organoids model human brain development and microcephaly Nature (2014) doi:10.1038/nature12517
Adapted from: http://www.insight.mrc.ac.uk/2015/07/20/eight-tiny-organs-grown-by-scientists/ accessed 31 August 2015