Regenerative medicine offers hope to millions of people worldwide and involves some of our most advanced biomedical science… and some apples. Here, Carlisle Baker-Jackson brings us the most promising and incredible efforts we have yet seen to grow tissues and organs. Cell, tissue or organ regeneration is, arguably, an idea that dates back millennia.

 

The modern day definition of regenerative medicine is attributed to Dr William Haseltine, a researcher well known for his work on genomics and HIV/AIDs. He suggested1 regenerative medicine was an approach to therapy that “employs human genes, proteins and cells to re-grow, restore or provide mechanical replacements for tissues that have been injured by trauma, damaged by disease or worn by time offering the prospect of curing diseases that cannot be treated effectively today, including those related to aging”.

 

Areas such as stem cell research, artificial organs and macrophage introduction also fall under the definition of regenerative medicine. The most well-known example of regenerative medicine is probably stem cells. Haematopoietic stem cells found in umbilical cord blood, for example, are used to treat childhood blood cancers. Adult stem cells can now be induced to become specialised stem cells (iPSCs) which are capable of being propagated indefinitely and, thanks to their ability to transform into any cell type, show incredible promise when being used to repair cells lost to disease or damage throughout the body.

 

Now researchers have the potential ability to grow various types of cell, the regenerative medicine community has naturally turned its attention to building whole organs. The many stem cell breakthroughs have allowed teams to seed them onto a vast range of natural, synthetic, biodegradable and permanent scaffolds that can then be placed into the body.Eelectrospinning, for example, is one method used to create these scaffolds – even though it was actually developed over a century ago2. The technique utilises high voltage to draw very fine fibres that dry and solidify forming nanometre-scale strands. Additive manufacturing, also known as 3D printing, can then be used to build layers from the strands until the final design is achieved.

 

Although initially used for creating just the scaffolds, additive manufacturing has also been used for another technique – 3D bioprinting. Incredibly, this technique alternates between printing a scaffold and a solution of live cells, known as bio-ink, inside that scaffold.

 

Using this approach, scientists at the Wake Forest Institute for Regenerative Medicine in North Carolina, US, announced in early 2016 they had successfully implanted bioprinted ear, bone and muscle structures3 into mice. Researchers at the Institute have been working in this field for over a decade – back in 2006 they successfully transplanted seven, non-bioprinted bladders grown from the patients’ own cells. The researchers took cells from the malfunctioning bladders of seven children with spina bifida and grew them on a biodegradable synthetic polymer and collagen mould. A separate layer of bladder urothelial cells were grown on the inside of the mould to create a working bladder4. The Holy Grail, so to speak, of 3D bioprinting is the production of complex organs. Although ‘simple’ tissues have been produced to great levels of sophistication, it is larger organs that are more troublesome. “It is complex solid organs such as the liver and kidney that will be most difficult to print,” says Professor Anthony Atala, director of the Wake Forest Institute. “These organs will require millions of cells and because they have high oxygen requirements, we must find ways to supply them with oxygen until they integrate with the body.”

 

The bioengineers at Wake Forest have designed their own integrated tissue-organ printer (ITOP) which can fabricate stable, human-scale tissue constructs of any shape3. This was the same printer used in 2016 that enabled them to create ear, bone and muscle structures. Bioprinting isn’t limited to just academia – companies such as Organovo are working on refining bioprinting human tissues and organs for research. Founded in 2007, their products include 3D printed livers, kidneys, and skin. They are aimed at companies exploring the effects drugs have on specific organs and could potentially reduce the need for animal testing. In 2015, they signed a deal with L’Oréal, allowing the company to understand more about its processes to produce skin at scale, prompting hopes that the technology could be used for more than cosmetic testing – possibly even burns research. Two weeks later they announced another deal with the pharmaceutical giant Merck, allowing the company use of their ExVive3D liver. The agreement also enables Merck to process other different organ models using Organovo’s 3D bioprinting technique. It is clear then, that the technology and know-how to grow tissues and organs is advanced. The task now is to make that tissue as functionally equivalent to the real thing as possible.

 

Advances in technology and science are constantly pushing the boundaries of regenerative medicine. From rebuilding teeth, to creating muscles better suited for transplantation, to assisting the regrowth of spinal nerves, regenerative medicine is advancing at such speed it is no longer wishful thinking.