A sustainable source of human stem cells is one of the holy grails of modern medicine.
With applications as broad as re-growing failed organs, fighting cancer, and stopping animal testing, stem cell therapy is predicted to be worth US$35bn by 2023.
Now, Cambridge startup bit bio, has a new approach to “re-coding” skin cells from adult humans, and rewinding the clock to give them the power of stem cells, and then turn them into whatever we want them to be – all without the controversial involvement of human embryos.
This, says neurosurgeon and founder Dr Mark Kotter, will “democratise stem cells”, so that anyone can use them, at any time.
The private sector is already placing big bets on the technology, with start-ups in the space raising as much as US$16mln in recent funding rounds.
A better future for drug discovery
Kotter says that our inability to produce enough human stem cells to match our need puts troubling limits on research and drug development.
“In drug discovery, the biggest bottleneck is the mismatch between animal models and animal cell lines used for drug discovery, and then human setting used in the clinical trial,” he explains.
Around 3% of new drugs make it all the way through trials and to market, he says, and the biggest reasons treatments tend to fail in clinical study is that they are either toxic to humans, or they don’t work.
“The only solution is to bring the human element back to the early stages,” says Kotter.
If new therapies were tested on human tissue first, it would reduce or even bypass the need to test on animals, as well as speeding up development.
Kotter founded bit bio, formerly known as Elpis BioMed, in 2016, in addition to startup Meatable, which produces meat by growing cultures in the lab, rather than rearing animals for the table.
The time is now for bit bio, because what it is doing has only been possible since a Nobel Prize-winning discovery twelve years ago, which turned the world of stem cell research upside down.
Kyoto University researcher Shinya Yamanaka proved that it was possible to take a mature human skin cell and reprogram it to be like the stem cell of an embryo.
Until this revelation, stem cell research had been dogged by controversy and expense, as scientists had to use human embryos and umbilical cords as a source of stem cells, and then simulate complex conditions inside the womb in order to make them develop into the cells they desired.
Coding for life
One big problem in early cell reprogramming was that stem cells are incredibly alert to invading DNA – and “silences” any foreign material it detects.
This meant that past attempts run a different program inside a cell often failed, because the cell destroyed it.
What happened next was a moment of “serendipity” in the lab, says Kotter.
Through trial and error, bit bio found they could use certain “safe harbours” where information is protected within cells, to stop the interference.
By taking the genetic switch for gene silencing and placing it inside a safe harbour, and then separately running the new cell program inside another safe harbour, scientists found they could override gene silencing in order to change the cell type.
This approach is what Kotter says makes bit bio unique.
The lab can produce up to a kilogram of human cells now, and its tech platform OptiOx has also proved that it can generate two human cell types with 100% accuracy.
Kotter says that now the range of cells able to be produced matters more than the quantity.
The company is now focused on discovering what separates one type of cell from another, which Kotter says will allow the firm to “decode the building blocks of life”.
To this end, bit bio is using machine learning to analyse the differences between every type of human cell, from bone marrow cells to liver cells, and create a reference map for all the different types.
Once the research is complete, the company hopes it will be able to generate any type of human cell, at scale, and with ultimate precision.
Buy and cell
Preparations are underway for a Series A funding round, and Kotter says that he is determined not to sell the business, having already rejected offers from would-be buyers.
Bit bio though is in an area hot with competition, which moves quickly.
A US$16mln Series A mega funding round was recently announced in October by another Cambridge start-up, Mogrify, which is hoping to master “direct cell reprogramming” and turn blood cells straight into brain cells, or any other type.
Mogrify uses big data to identify the small molecules needed to convert, maintain and culture a target cell type.
While both companies were finalists in the 2018 Cambridge Startup of the Year award, bit bio was the one to scoop the prize.
One aspect that separates the two companies is that Mogrify uses its technology to turn cells directly into other cell types, rather than using it to rewind to the “stem cell” phase, which is when cells can reproduce very quickly,
Kotter says that this stem cell phase focus is what allows bit bio to have a stable supply of human cells.
If bit bio completes a similar, or even bigger, fundraise, it could advance the fledgling firm from seed to stem, in its attempt to stabilise a production line for essential cell technology.