Feature: Custom stem cells

One of Paul Verma’s primary goals is to produce autologous stem cells, or cells that are immune-compatible with a particular host. Even if stem cells prove to have regenerative applications, there’s no point injecting any old stem cells into a patient.

Our immune system is wise to such tricks and will rapidly hunt down and eliminate the foreign ‘invaders’ in most instances. As a result, current experimental stem cell therapies require immunosuppressive drugs in order to work – which is far from ideal in the long term. Having a bank of autologous stem cells, or the ability to produce them on demand, would be ideal.

However, there are still a number of significant milestones to be reached before we can produce such autologous stem cells to treat specific ailments, such as type 1 diabetes or Friedreich’s ataxia.

“It’s going to take a long time before we can produce a patient-specific cell and get it through all the regulatory hurdles,” says Verma.

According to Verma, a crucial first stage is to actually master reprogramming the cell. “That understanding is going to allow us to recapitulate diseases in a dish and see what goes wrong.”

The idea is to produce iPS cells from an individual with type 1 diabetes. Then take these embryonic stem cells and mature them into insulin producing beta cells. “You can then try to recapitulate the disease and see what happens to the cell, and what can we do to modify them to prevent the attack from the immune system.”

Once that progression is better understood, these cells can be used as a test bed for drug discovery. “The second stage, once you can see what’s going wrong, is to try some drug intervention to see if you can arrest or slow down the progression of the disease,” says Verma.

The final stage would be to produce cells – healthy insulin producing beta cells in the case of diabetes – that are actually able to be transplanted back into the patient.

Another disease Verma’s lab is looking at in collaboration with Dr Alice Pebay (O'Brien Institute) and Dr Mirella Dottori (University of Melbourne) is Friedreich’s ataxia, which affects the nervous system and muscles. The end goal here would be to produce healthy cardio and nerve cells.

However, Verma warns there’s a long way to go before we are able to produce made-to-order autologous stem cells. As he points out, most studies with stem cells to date have worked with mouse models. “But a mouse lives for a year or two at the most.”

According to Verma, if long-term safety and efficacy are in question, you need to perform your studies in longer-lived animals. As a result, his lab has been developing iPS cells from large animals, such as horses, cows and sheep. “Then, using an iPS cell or embryonic stem cell from that species, set up therapeutic experiments and see long term if we get efficacy and safety.”

Even once the stem cells are shown to the safe, that’s not the end of the challenges in bringing them to the therapeutic arena. Currently there are only a very limited number of stem cell lines, which is fine for experimental use, but if you want to develop stem cell therapies that are immune compatible with a wide range of patients, the number of cell lines will need to be dramatically increased.

One option is to develop stem cells from the patient on an ad hoc basis, but this is cumbersome and expensive. A more economical approach, says Verma, is to have stem cell banks that have a wide range of cell lines that can be immunomatched to patients. The trick is to get a range of cells that offer the broadest range of immunocompatability with the general public.

“That’s where the significance is of using iPS or SCNT cells comes in,” he says. Using these technologies you can build banks with a predetermined range of genetics to accommodate the broadest spectrum of patients. “You pick the best cell lines that are most representative of the population, so you can then get a very close match for the cells in the patient.”

Bespoke stem cells might still be a way off, but the potential therapeutic benefits will be well worth the wait. If Verma’s vision plays out, one day a diabetic might be able to make a ‘withdrawal’ from the stem cell bank, and have them differentiated into beta cells that are as good as autologous stem cells. If Dolly the sheep was an eye opener, imagine the impact that technology will have.