To engineer a new heart, first you take a pig…

This week the prestigious science journal Nature carries two fascinating reports on the progress being made in the exciting field of tissue engineering that we recommend to our readers – both are open access so you don’t need a subscription to Nature to read them.

The first is a feature article by Brenden Maher entitled “Tissue engineering: How to build a heart” which focuses on the research being done by Doris Taylor  at the Texas heart Institute and  Harald Ott at Massachusetts General Hospital in Boston. He also discusses research being done on other tissues, including several that we have discussed on this blog, such as relatively simple tissues like bladders, tracheas and blood vessels which are already being trialed in patients, and more complex tissues such as lungs that require more laboratory research before they can move to the clinic. Brenden Maher’s article, and the accompanying video and podcast, are an excellent overview of this exciting field.  It’s an overview that highlights the key contribution of animal research, not just the provision of the raw material, the decellularized pig heart scaffolds upon which new organs can be built and the stem cells used to seed these scaffolds, but also the evaluation and continuing refinement of the artificial organs and tissues produced.

The second article “Miniature human liver grown in mice” by Monya Baker provides another example of how the field of tissue engineering is progressing. There have been several previous attempts to create artificial liver tissue in the laboratory, but this is the first time that an engineered liver has been produced that is vascularized and when transplanted into a mouse model of liver failure was able to connect with the mouse blood vessels and function as a liver.

Like the heart grown by Harald Ott, the artificial liver buds were produced by Takanori Takebe and colleagues were created using induced pluripotent stem cells (iPS cells), but rather than using a scaffold they found – after hundreds of experiments – that if they mixed iPS cell derived liver precursor cells with other stem cells that develop into tissues such as blood vessels, and got the ratios of cells and conditions just right they would self-organize and develop into a functioning liver bud.  It’s an example of why scientists need be able to use a wide variety of approaches in tissue engineering, the technique that works best for the heart may not be best for the liver, while another technique again might work best for the trachea.

Studies in mice were key to the assessment of engineered mini-livers

This artificial liver bud holds great promise for use in transplant operations, though before that becomes a reality the liver buds will need to be studied for longer times in mice to ensure that they continue to function over extended periods and do not develop abnormalities such as cancer, and the technique needs to be improved in order to produce the far larger amounts of liver tissue required for human transplants. In the shorter term the liver buds may have a role in preclinical screening of new drugs, as the initial studies in mice reported by Takanori Takebe and colleagues (1) demonstrated that when the mice were given a range of small molecules – including two drugs they are metabolized differently by human and mouse livers -  they produced a metabolic profile that closely resembled that of an adult human liver. It is also likely that this liver bud technology, or a derivation more suitable for high-throughput screening, will be used to screen chemicals in vitro, reducing the number that need to be evaluated in live animals later.

It’s a great window on an exciting area of 21st century medicine, one that we will all be hearing about a lot over the coming years.

Speaking of Research

1) Takanori Takebe et al. “Vascularized and functional human liver from an iPSC-derived organ bud transplant” Nature (2013) doi:10.1038/nature12271