Artificial organs – grown in the lab and transplanted into someone’s body – have been on the horizon for some years now. They present many challenges but, if we can overcome them, they will open up the possibility for patients who need a new organ no longer having to wait for a human donor. They will also save health services money, eliminating the high costs that accrue during years of treatment, especially for some chronic conditions.
In 2021, we will see significant breakthroughs around how artificial organs function, while the technology used to produce them will take them one step closer to use in the clinic.
To date, the greatest success we have had in this field has been the production of lab-grown epidermis, the outermost layer of skin, to replace that which has been destroyed by burns. This is achieved by growing the stem cells of a patient’s own epidermis (from an area spared by the burn) in culture and then transferring their progeny on to a thin layer of fibrin, which is then transferred on to the affected surface. The new epidermis attaches and functions for decades, although it is unable to produce hair or sebaceous glands. This technique has saved the lives of thousands of burns patients and is in use in hospitals across the world.
But we can go further than that. In 2017, Michele De Luca and Graziella Pellegrini at the University of Modena in Italy, corrected the DNA in stem cells taken from a child with epidermolysis bullosa, a chronic ailment that makes the skin prone to painful tears. Through a combination of stem-cell and gene therapy, they were able to graft new in-vitro-grown epidermis on to his body, curing him of the devastating genetic disease.
Five years after their intervention, the child’s skin is still normal and authorisation has been requested to use the technique to treat other forms of this disease.
In 2020, Karl Koehler and his team at the Boston Children’s Hospital were able to use human stem cells to grow the whole thickness of the skin, rather than simply the epidermis. This will allow other medical teams to treat those diseases or injuries that also affect the dermis, the inner layer of the skin. Some time will still be needed, however, before seeing this entering experimentation, as clinical-grade scale-up will be needed first.
In 2021, we’ll see other organs grown. In my lab at the Francis Crick Institute, we’re creating an artificial thymus, entirely reconstructed from cultivated human stem cells.
The thymus is crucial for the development of cells called T lymphocytes, which fight off and destroy infectious agents or cancerous cells. Some children are born without a thymus, making them intensely vulnerable to infections. A new organ would offer a route to a normal life. The thymus is also distinct among all organs as it helps lymphocytes recognise and therefore not harm our own healthy cells. Potentially any transplanted patient could benefit from an artificial thymus grown from the donor’s stem cells. This would reset the patient’s immune system so it recognises the donor organ as if it was their own, eliminating the need for life-long immune-suppression drugs.
Growing an organ isn’t easy, though. Technicians need to ensure that stem cells turn into the correct type of specialised cell needed for a specific organ, and that these are in the right proportions and position. In 2021, we’ll see more of the technology needed to grow complex organs. Researchers in many laboratories are working on improving bioreactors – machines that provide the precise conditions, such as temperature, humidity, nutrients, oxygen and movement, needed to create organs and mimic their function in the body.
In 2021, researchers will also expand our knowledge of stem cells. In my lab, for example, we are working on an artificial oesophagus to better understand how these cells behave in order to develop the organ’s complex structure that ensures its physiological function.
Next-generation DNA sequencing also allows us to decipher rapidly and with extreme precision which genes are expressed in a given tissue and to what extent. This means we can uncover exactly how artificial body parts compare to natural ones, which is a crucial issue, especially as we want these new organs to last a lifetime.
Paola Bonfanti is group leader of the Epithelial Stem Cell Biology & Regenerative Medicine Laboratory at the Francis Crick Institute