OTT LAB, CENTRE FOR REGENERATIVE MEDICINE, MASSACHUSETTS GENERAL HOSPITAL

An engineered kidney transplanted into a living rat has been shown to successfully filter blood and urine -- though at a fraction of a normal kidney's functionality.

The groundbreaking study, published in the journal Nature Medicine, provides some distant hope for the 51,000 people in the UK in need of dialysis or an organ transplant. Receiving an organ from a living donor, often a relative, gives patients the greatest chance of success with survival rates about ten percent better on average. However, according to NHS statistics just 1,009 living donor kidney transplants took place in the year preceding March 2012, with under 3,000 transplants taking place in total. As donor shortages persist and those in need of dialysis or transplant increase (up 20 percent since 2006) Kidney Research UK made the announcement this year that kidney disease threatens to become a public health crisis in the near future.


This is why regenerative medicine and stem cell technology has played such an important role in organ transplant research in recent years. If successful -- as it has been with hollow transplants such as tracheas and bladders -- it could pave the way for solid organs engineered from an individual's own cells, thus eliminating the chance of rejection and the need for potent immunosuppression drugs.

The latest experiment, led by Dr Harald Ott of Massachusetts General Hospital, follows-up from a series of successful attempts by Ott to engineer a beating heart and transplant engineered lungs into rats. These studies were all based on a technique developed by Ott and colleagues in 2008 called whole organ decellularisation. This involves stripping an organ back to its building blocks using a detergent, then growing new, healthy progenitor stem cells onto this empty, scaffold-like structure that holds everything together. Ott literally went from A to Z in the lab, trialling different chemicals that would effectively strip an organ but leave the scaffold membrane intact -- some caused organs to disintegrate, others caused it to morph and change shape. Turns out, the key was something fairly mundane -- Sodium dodecyl sulphate, a compound used in toothpaste and shampoo.

Read next Stem cell breakthrough restores eyesight in blind rabbits Stem cell breakthrough restores eyesight in blind rabbits

Using the same technique Ott stripped back all the cells from kidneys from recently deceased rats to leave a translucent structure. These were then flooded with blood vessel cells from humans and kidney cells from newborn rats. These were left to grow in a bioreactor for 12 days, by which time the cells had entirely covered the shell organ. At this point, urine production was about 23 percent that of natural urine production, however post-transplant this functionality dropped to 5 percent.

The procedure means that one day donated organs that are not a match could be stripped back and repopulated with a patient's own cells, rendering made-to-measure organs unlikely to be rejected. "I know Harald Ott quite well and he is a great surgeon and a great scientist," Paolo de Coppi, research leader at Great Ormond Street Hospital and the man behind the first transplant of a trachea grown from a patient's own cells, told Wired.co.uk. "I believe he is showing us that not only simple organs, like the trachea we have transplanted, are possible, but that the future looks even brighter and we can hope to engineer more complex organs such as the kidney."

Elaine Davies, head of research operations at Kidney Research UK points out that besides the great potential for hope the study provides, "regenerative medicine is still in its infancy for kidney disease, because the kidney represents a far more complex organ to be able to replicate its anatomy and physiology compared with other organs in the body."


Although replicating five percent functionality is an incredible feat (Ott told the BBC that those on dialysis would need just 10-15 percent functionality to get back their independence), building a human kidney, one of the most complex organs in the body, is a big leap from building a rat organ. The team needs to ensure the organ will last and keep on replicating cells normally, and get functionality up. The engineered lung transplants in rats also only lasted for six hours, and carried out gas exchange for just two of those.

Speaking to Wired.co.uk, professor of regenerative medicine bioprocessing at UCL Chris Mason argued that getting the biology right only gets Ott's team part way to the finishing line -- finding a way to pay for efficient manufacturing processes to take the technology to those that need it could yet hold up progress. "The biggest challenge, even when the team get adequate performance in their rat model will be the manufacturing," Mason said. "The scale of the challenge (each kidney will require approximately 10,000,000,000 cells) and the cost will both require major step changes in manufacturing capability. Currently, our manufacturing ability is at least two orders of magnitude below the goal of having bioengineered kidneys available for routine clinical practice at a cost that would be acceptable to the payers. A considerable investment in innovation manufacturing techniques over several years will be needed if this approach is to provide a workable solution for patients, healthcare providers and society."

Nevertheless the technology will be a game changer. A decade ago, it's unlikely we thought replacing windpipes or bladders with our own cells would be on the agenda, but today the success of those procedures has been duly proven. Ott's colleague Joseph Vacanti has previously argued that artificial scaffolds will pave the way for organs "made on demand, with low-cost materials and manufacturing technologies". Tubular structures like tracheas could be built this way, but complex solid organs such as kidneys and hearts would benefit from 3D printing, he argued. In the meantime Ott's team could experiment with replacing a rat's kidney with its own stripped and repopulated organ, or with repopulating animal organs such as pig's hearts with human cells.