Early work on lab-grown liver tissue

“Grow-your-own organs” could soon be a reality, claims the Daily Mail, which says that “scientists have grown a liver in a laboratory” using stem cells. The newspaper says the research could offer “fresh hope to hundreds of thousands of patients with diseased and damaged organs”.

This was innovative research, albeit at a very early stage. However, many newspapers have overstated the significance of the findings at this time, and it is too soon to proclaim this as a solution to the shortage of suitable organs for transplants.

The laboratory study in rats is based around stripping an existing liver down to a ‘cellular scaffold’ that retains the basic underlying structure of the liver. This is then taken over by cells from the recipient, resulting in a compatible liver graft (not yet a whole liver) that could be used for transplantation.

The methods that these researchers have developed will pave the way for further research and may one day lead to technologies that can be studied in humans. The lead researcher is quoted as being "cautiously optimistic", acknowledging that there are further hurdles to overcome.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School and other medical and academic institutions in the USA, Japan and Israel. The study was funded by grants from the US National Institutes of Health and the US National Science Foundation and was published in the peer-reviewed medical journal Nature Medicine.  

The implications of these findings have generally been overstated by the newspapers. While this is certainly a piece of innovative and important methodological research, it is a gross over-simplification to suggest that the study ‘grew a liver’. It is also premature to suggest that it could solve the organ transplant shortage given the very preliminary nature of this research.

What kind of research was this?

This was research conducted in the laboratory and in rats. Researchers were investigating new technology to establish a viable graft for liver transplantation, looking at techniques that may, in time, help us to develop replacement organs for human transplant.

The basic concept behind this experimental technology is to strip an organ down to its basic cellular skeleton and then infuse the skeleton with stem cells from the intended recipient. These stem cells then repopulate the scaffold, re-establishing the organ as a healthy, compatible source of liver tissue for the recipient. This technology would, in part, rely on the properties of stem cells, which are cells that are at an early stage of development and, therefore, still have the ability to turn into any type of cell in the body.

The liver is a complicated structure and the researchers report that the development of a tissue-engineered organ is limited by the need to establish an appropriate oxygen and nutrient transport system. In looking at new ways to produce viable liver tissue they made use of this scaffold technique, which leaves the blood vessels intact, thereby conserving the donor liver’s structures for transporting oxygen and nutrients.

What did the research involve?

The researchers based their investigations on a technique of ‘decellularization’, which has been developed and previously used to prepare scaffolds for tissue engineering. The cells are stripped from an organ, leaving the organ’s cellular architecture, which, in principle, can be reseeded with stem cells. These scaffolds retain the original connective tissue (for example, proteins such as collagen) and also the vascular structure that can, in principle, be reconnected to the circulatory system.

The study authors report the details of the methods they used to remove the cells from the livers of rats to create these scaffolds. They were also able to show, by injecting dye, that the scaffolds retained the vessels of a normal liver as the dye could flow from the bigger vessels to the smaller microvessels.

They then set about ‘reseeding’ the scaffold, by introducing liver cells into the structure. They introduced about 12.5 million cells in each of four rounds of reseeding, with 10-minute intervals between each round. They then continuously perfused the organ for five days (i.e. flushed it with cells) to distribute the cells throughout the scaffold.

The researchers then determined whether the liver grafts would function when transplanted into rats. They established a blood flow in the new graft by attaching it to the rat’s blood supply and left it there for eight hours before further analysis. After this time the function of the graft was assessed by flushing the graft with rat blood outside of the body for a further 24 hours.

What were the basic results?

The researchers report their results in great detail, describing the cellular structure, the positions in which cells were distributed throughout the new organ, the enzymes present and the metabolic activity in the cells. They say that the decellularization and reseeding of the rats’ livers was largely successful. The graft also successfully filled with blood when connected to the rat’s artery and veins, with minimal damage to the new cells after the graft was connected to the rat’s system.

How did the researchers interpret the results?

The researchers report that their study is the first step towards the development of “recellularized liver matrix” that could be used as a graft for transplantation. They say that, while previous attempts have failed, they have demonstrated a method that could preserve the 3-D structure of the organ and its vessels, membranes and connective tissue.

Conclusion

This laboratory study has developed a way of establishing a cellular scaffold that both retains the basic underlying structure of the liver and allows seeding with new cells to establish a potentially viable liver graft. This innovative research is a big initial step towards overcoming some of the problems that make the development of engineered tissue transplants such a challenge. It is likely that the methods that these researchers have developed will pave the way for further research in this area, and may one day lead to technologies that can be studied in humans.

While this is an important advance in the field of bioengineering, there is still a lot more work left to do, and it is too soon to proclaim this as a solution to the organ transplant shortage. The lead researcher is quoted as being "cautiously optimistic", acknowledging that there are still hurdles to overcome. Future studies need to determine whether the graft can function as a normal liver, particularly in the longer term, as the rats in this study did not have their functioning livers removed and were only implanted with their liver grafts for eight hours.

The researchers acknowledge that more needs to be done before an entire liver can be reconstituted, including the addition of a variety of other types of specialised cells. They are undertaking further research to optimise some of the methods they have established in this preliminary study. As they conclude themselves, “further studies are required to determine whether the techniques described here can be scaled up for use in humans”.