Ghost Heart

Decellularisation methods could provide organs to relieve an over-subscribed waiting list for solid organ transplant and reduce the demand for immunosuppressive drugs.

(This is an abridged version of an article I wrote in March 2014 titled 'Playing Prometheus' - shorter, (hopefully) more artful, this version is better adapted to sharing.)

For those facing end-stage organ failure, the only option currently available is organ transplantation. Though more and more people are becoming aware of the importance of joining the organ donor register, there are currently just under 7,000 patients on the waiting list for a solid organ transplant and the need for organs still far exceeds the number of donor organs. Hundreds of patients die while waiting for a transplant, or are removed from the transplant waiting list as a result of deteriorating health. Huge numbers of people are still suffering due to a shortage of organs, and this is not the only complication.

When an organ is transplanted, the recipient’s body recognizes the cells as foreign and will try to attack it, thinking it a disease-causing pathogen. The new organ could be destroyed unless drugs are given to suppress the patient’s immune response. Yet these immunosuppressants can make the body vulnerable to opportunistic infections. Receiving a donated organ does not necessarily spell the end of a patient’s health complications.

Many films and novels have explored possible repercussions of organ donor shortages, including the depiction of dystopian worlds where ethically-dubious industries have emerged to profit from the situation. Science fiction has pursued possible solutions: some within the possibilities of current scientific development; some stretching the boundaries. These stories are peppered with elements of horror, audiences gaining reassurance that these practices will be possible far into the future.

They may come sooner than expected.

New solutions for organ transplantation, involving tissue engineering and even whole organ engineering, are being pursued, with amazing results. The growth of relatively simple tissues, including blood vessels, urinary bladders and trachea, has shown great development in recent years. However, these organs don’t require a large vascular network to be functional. Producing more complex organs, such as lungs, livers, kidneys and hearts brings a new set of challenges.

Vascular networks in human organs allow nutrient and gas exchange. They are understandably complex and difficult to reproduce from artificial materials. Decellularisation techniques are being employed to strip natural solid organs of their living cells. This leaves an intact structure with an accurate and functional vascular system. This structure is called the extra-cellular matrix (ECM) and acts as a scaffold on which new cells can be grown. It’s vital that the decellularisation process doesn’t destroy or damage this matrix, as it will give structural integrity and biological signals to the new organ.

The decellularisation process involves the destruction of living cells, by repeatedly freezing and thawing the organ, and exposing it to detergents. Detergents must be known not to affect the integrity of the protein in the extra-cellular matrix tissue. Before the next step, the organ is observed using imaging techniques to ensure the decellularised organ’s vascular structure remains intact.

The next step is recellularisation, involving the growth of new cells on the extra-cellular matrix. There are a variety of cell types under investigation as potential candidates for this process. The cells would need to be easily isolated, grown rapidly and cost-effectively, and easily prompted to differentiate to various cell types. Ideally, a sample of the patient’s own cells would be used, so that the organ would be less likely to be rejected by the body after transplantation, reducing the need for immunosuppressive drugs.

Some complications mean this decellularisation process is still a long way from having its successes translated to the clinic. Most importantly, an optimal source of donor organs needs to be found. So far, rat, pig and mouse organs have been experimented with. It appears we may soon see transplants of pig-human hybrid organs, as porcine acellular matrices are similar in size to human organs and provide a low risk of transmission of infectious agents.

The stripping of a real, functioning organ of its living cells to ‘reanimate’ for further use in another organism seems like an idea pulled straight from science fiction or horror. This could be compared with the attempts made by Victor Frankenstein to reanimate dead tissue in Mary Shelley’s 1818 novel Frankenstein. However, these amazing decellularisation methods are far from threatening. They have the potential to save lives, providing organs for those in need and reducing the need for immunosuppressive drugs.

Frankenstein’s creature is originally benevolent and peaceful, but is rejected for its appearance and driven to become the monster society believes it to be. The analogy could be applied to these decellularised organs; the process can save lives and improve others, though it is likely to be met with a certain degree of caution and even repulsion. The only hindrance to its success may be our inability to accept it. If we can overcome our fears and understand the great benefit of these techniques that might at first repulse or frighten us, then we are likely to see life-changing results.

References & Further Reading

• Shelley, "Frankenstein; or, The Modern Prometheus", Lackington, Hughes, Harding, Mavor & Jones (1818).
• Arenas-Herrera et al, "Decellularization for whole organ bioengineering", Journal of Biomedical Materials (2013).
• Moran et al, "Whole-organ bioengineering: current tales of modern alchemy", Translation Research - Journal of Laboratory and Clinical Medicine (2014).
• NHS Organ Donation Website.

Listing image: RMR Labs, Texas Heart Institute