Stem cells are our bodies’ production line. This one type of cell churns out the embryos that grow every other specialist cell in our bodies, from muscle, blood and tissue cells to the neurons that are the seat of human consciousness. For years, scientists have immersed themselves in their study, in the hope of learning exactly how stem cells work.

Understanding the finer functions of what makes a stem cell produce one kind of cell rather than another would potentially be the key to being able to repair or regenerate every part of our bodies. Countless laboratory hours and hundreds of millions of dollars have been spent in the pursuit of learning how to harness the incredible power of stem cells. The prize, a production line creating any cell or combination of cells, for example a whole human organ, holds the potential to have a transformative effect of medicine.

Until now, stem cells have proven themselves reluctant to be controlled and manipulated, holding on to most of their secrets, though progress has been made. But British biotech start-up Bit.Bio, claims to have made a stem cell breakthrough that allows its scientists to reliably reprogram stem cells to do their bidding.

The biotechnology looks promising enough to have attracted £40 million of investment and prompted a new partnership with the London Institute for Mathematical Sciences. The company and Institute will cooperate in trying to further understand and replicate the biological programming used by human cellular biology.

Bit.Bio was founded by Cambridge neurosurgeon Mark Kotter who comments on what his company’s research could ultimately mean:

“You can turn cells into computers where you can just invoke a new programme and force them to take up a new identity. That’s a huge paradigm shift”.

 Bit.Bio’s biotechnology is already being applied to stem cells to programme than to create over ten different types of cells has potential application in drug discovery, cell-based therapies and eventually building, or ‘growing’, whole organs for transplant.

The theory that living cells can be programmed as though DNA were the equivalent to a computer language is still a controversial one. The genetic code held in a neuron is exactly the same as that in a kidney or heart cell. But the body differentiates cells through proteins called transcription factors. These specialist proteins express or supress the right genes in the full code held in each cell so they specialise in their function and role.

Over the past decade or so, scientists have discovered how to convert body cells back into their stem cell state. But until now, managing to control how they then differentiate has proven elusive.

Until now, the approach has been to attempt to reverse engineer the stem cell differentiation process by recreating the environment in which different stem cells develop into different body cells. To make bone cells, for example, stem cells are placed in an environment that is an exact replication of the chemical and mechanical environment that surrounds a bone. The stem cells are jolted and pushed around as they would be in the body as the form a bone cell embryo.

It is, however, a very labour and time intensive approach. An alternative development has been to activate the transcription factor proteins that directly identify a particular cell type. But activating the right programming is difficult and imprecise. Cells tend to respond by ‘gene silencing’ genes newly activated in this way.

BitBio’s new technology takes a different approach and is based on University of Cambridge research first published 3 years ago in the Stem Cell Reports journal. The research uncovered that embedding transcription factor programs into specialist areas of the genome prevented gene silencing. Machine learning techniques are being used to screen cells to identify the transcription factors that result in the production of different cells.

Professor Kotter explains:

“What we do is we just switch on the programme from the inside. You get quicker by an order of magnitude, so we get into brain cells in 4-5 days, immune cells in seven days. And that compares to maybe 60 to 100 days.”

It will still take many years of research, not to mention regulatory approval, before growing human organs to order is a realistic prospect. Not only would the right cells have to be produced by programmed stem cells, but they would have to arrange themselves, or be arranged, in the correct way. Not all experts are convinced that BitBio’s biotech will prove applicable to every kind of cell. Dusko Ilic, a stem cell biologist at King’s College London “would not put my money on it”.

But others have, with investors including the billionaire Yuri Milner backing Bit.Bio to the tune of £40 million. Profession Kotter also argues that focusing on the progress that still has to be made before organs might be produced misses the point of what has been achieved. He believe the ability to produce even individual cells to order opens up completely new possibilities and areas of scientific exploration:

 “What we can also do is find novel combinations and combine programmes of different cell types, so you can make weird cells that have traits from various different cell types.”

One area of focus is plans to attempt to ‘tweak’ and combine immune cells in ways that would make them more powerful, or effective in fighting off particular infections:

“You could you could imagine this in the context of regenerative medicine or in the context of cancer killing,” he said. “We could make cells that right now don’t even exist.”

The UK’s Stem Cell Biotech Champions

Bit.Bio is not the only British biotech start-up working towards potentially ground breaking stem cell research. Some of the most exciting young British companies in the space include:

ReNeuron

AIM-listed ReNeuron is involved in the research and development of stem cell technology for the treatment of motor disabilities and blindness-causing diseases. The company is also in the process of running phase II clinical trials for a stem cell-based therapy for the treatment of patients left disabled by a stroke.

A third research direction being pursued by ReNeuron is an ecosomes platform which focuses on using non-sized exosome particles, which facilitate communication between cells through the transfer of RNA and DNA molecules, as a potential vector for the delivery of drugs. As stem cells expand, large numbers of exosomes are secreted into the culture media. Once purified, the exosomes, says ReNeuron, can be modified and loaded with drugs, which they then deliver to targeted, hard-to-reach areas of the body.

Mogrify

Another member of the Cambridge biotech cluster, Mogrify® has developed a proprietary suite of platform technologies that use big-data to inform direct cellular conversion  and the maintenance of cell identity.

The platforms use next-generation sequencing, gene regulatory and epigenetic network data to predict the transcription factors and culture medium conditions required to produce any target cell type from any source cell type. An alternative to the Bit.Bio approach.

Mogrify says its platform can be used to enhance existing stem-cell forward reprogramming methods or even to potentially bypass development pathways entirely, affecting a direct transdifferentiation between a mature cell type to another mature cell type.

The end goal is the development of ex vivo cell therapies and to pioneer a new class of in vivo reprogramming therapies for indications of high unmet clinical need in hematological, immunological, ophthalmological and other disease areas.

The biotechnology company has raised over $20 million from investors including Ahren Innovation Capital, Parkwalk, 24Haymarket, Dr. Darrin M. Disley, OBE and the University of Bristol Enterprise Fund III.

Cell Guidance Systems

Cell Guidance Systems is an early stage start-up that has so far attracted a relatively modest £1.5 million in funding to further its research into ensomes-based protein delivery systems. Also part of the Cambridge biotech cluster, CGS was founded in 2010 and has to date developed the following stem cell-based biotech:

• PODS® – a depot technology which expands the flexibility and utility of proteins, such as growth factors
• Pluripro® media – for human pluripotent cell maintenance
• IVC Medium – for maintaining blastocysts
• ETS-Embryo medium – for the establishment of “artificial” embryos
• Products for exosome research – products to purify, track, assay and measure exosomes