Organs for growth

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In the UK alone, one thousand individuals in need of an organ transplant die every year due to the shortage of availability. This crisis not only costs lives, but has also led to a substantial increase in the demand for alternative treatments. Advances in molecular diagnostics could enable detection of lethal diseases before clinical manifestations occur, which would facilitate pre-emptive transplants, but this is likely to only increase the demand for organs.

To address this issue, researchers are working on novel techniques that are moving the field of organ transplantation into uncharted territory.

The ability to grow human body parts was thought an insurmountable task, but scientists across the world are starting to get positive results. Although it’s clear that we’re still a long way from transplanting lab-grown lungs or livers into patients, there is reason to believe that this could be a plausible future for organ transplantation.

Two years on from the implant of a synthetic blood vessel into four-year-old Angela Irizarry, all is well. Scientists coated a biodegradable tube with stem cells harvested from the child’s bone marrow and the subsequent graft successfully treated her heart defect. The technique used 3D printers, and created scaffolding structures that fully supported the patient’s stem cells.

With traditional methods, one of the greatest problems facing scientists is the chance that the body may reject the donated organ. This occurs when the body’s immune system, specifically the T-cells, recognise the cells from the transplanted organ as ‘non-self’ and so attack and ultimately destroy the alien organ. To prevent this, post-transplant patients have to take immunosuppressant drugs that leave them highly susceptible to infection – to the point where transmission even of the common cold can be extremely dangerous.

The beauty of growing new parts in the body is that, as in the case of Angela Irizarry, the stem cells are taken from the patients themselves; meaning that transplantation doesn’t hold the same fear of rejection and that patients don’t need to continuously take debilitating immunosuppressants.

Dr Paulo Macchiarini, a Professor of Regenerative Surgery in Sweden who pioneered this procedure, has now carried out six life-saving operations through windpipe transplantation. In each, scaffolds were bioengineered and stem cells from the patients were grown over the top of them. It was initially believed that stem cells had the ability to differentiate into the appropriate cells once transplanted into the region. Surprisingly, it appears that this is incorrect. Studies in mice showed that the original seeding cells die relatively quickly, and it is the incoming cells from other vessels that are the cause of the transplant functioning normally.

Although this works well for single blood vessels and windpipes, it’s much harder to achieve for more complex organs. In response, some labs are trying to overcome organ rejection by washing the cells off organs before transplantation leaving only the natural scaffolding structure, which they cover with a patient’s own cells. Using this technique, it is theoretically possible that a pig organ matrix painted with human cells could be successfully transplanted. The transfer of an organ from one species to another is called Xenotransplantation and dates back to the 1980s. Pigs are a common focus as they have organs that are anatomically similar to our own. Until recently, tests have been incredibly unsuccessful with extremely high fatality rates, but this new protocol opens exciting doors for the field.

An alternative to transplantation is dialysis, where the function of an organ is replaced by a machine that is external to the body. Currently, this is normally only used when a patient is waiting for a donor, but recent developments show that a scaled down dialysis machine could function as a completely artificial organ. Work in this area gained a widespread following after How to Build a Bionic Man aired on Channel 4 in February. The documentary showcased the cutting edge of prosthetic limb and artificial organ research. Arizona based company SynCardia Systems Inc. now offers an entirely artificial heart that replaces both failing ventricles and all four heart valves. To date, the longest a patient has been supported by the artificial heart is just under four years, suggesting that this is a very conceivable future for organ transplantation.

Other work in the field looks at techniques that ensure donor organs are up to standard. The problem originally faced by surgeons was that tissue degrades so quickly once removed from the body that immediate transplantation is crucial. Furthermore, particularly fragile organs like lungs can be damaged when a patient dies with the result that only about 15% of donated lungs actually being usable.

A machine developed by Dr Shaf Keshavjee in 2008 not only permitted lungs to remain viable ex vivo for an extended period of time but also made it possible for doctors to ‘enhance’ the organ, leaving it healthier than its pre-transplant state. Whilst in the machine, doctors can study the anatomy of the lung using fibre optic cameras and also deliver therapies to targeted areas. It is believed that this technique will not only help organs remain viable for transplantation for two to three days, but will also massively increase the number of organs that are suitable for donation.

With an ageing population, illnesses like heart failure and liver disease will compound the problem of high demand for organs but with the new methods on the horizons, it would be rational to believe that we’ve a chance of coping with the problem. The collaborative works of medics and bioengineers forecast a future where lab derived or manipulated body parts are commonplace. The field has extremely exciting prospects and will, no doubt, be instrumental for the health of the global population in the coming decades.

 

IMAGE: shaunamey

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