A “revolutionary” new approach to creating stem cells in the laboratory could open up a new era of personalised medicine, it is claimed.
Scientists have shown it is possible to reprogramme cells into an embryonic-like state simply by altering their environment.
It means in principle that cells can have their developmental clock turned back without directly interfering with their genes – something never achieved before.
The cells become “pluripotent”, having the potential ability to transform themselves into virtually any kind of tissue in the body, from brain to bone.
Reprogramming a patient’s own cells in this way is seen as the Holy Grail of regenerative medicine, raising the prospect of repairing diseased and damaged organs with new healthy tissue that will not be rejected by the immune system.
Current methods of performing the same trick involve genetic manipulation, which carries with it a serious risk of triggering cancer.
But the new method described in the journal Nature requires no genetic tweaking. Scientists simply bathed immature white blood cells from mice in an acidic solution for 25 minutes.
Tests showed that, stressed in this way, some of the cells lost their “blood identity” and produced gene markers typical of early embryos.
When these cells were transferred to a special growth-promoting culture medium they began to multiply and acquired features typical of embryonic stem cells.
After being injected into embryos, they contributed to the body tissue of baby mice.
The scientists, led by Dr Haruko Obokata, from the Riken Centre for Developmental Biology in Kobe, Japan, named their creations “Stap” (stimulus-triggered acquisition of pluripotency) cells.
Commenting on the research, Dr Dusko Ilic, a reader in stem cell science at King’s College London, said: “The approach is indeed revolutionary. It will make fundamental change in a way how scientists perceive the interplay of environment and genome.”
Colleague Professor Chris Mason, chair of regenerative medicine bioprocessing, at University College London, said: “If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient’s own cells as starting material – the age of personalised medicine would have finally arrived.”
He added: “Who would have thought that to reprogramme adult cells to an embryonic stem cell-like (pluripotent) state just required a small amount of acid for less than half an hour – an incredible discovery.”
The Japanese and US team was inspired by examples from nature where the physical environment appears to alter cell identity.
Temperature helps determine the sex of crocodile embryos, for instance, while frog cells fated to form skin develop into brain tissue if exposed to acidic, low pH conditions.
In plants, environmental stress can reprogramme mature cells into “blank slate” cells capable of forming whole new structures including roots and stalks.
Although pluripotent embryonic stem (ES) cells can be “mined” from discarded early-stage human embryos, this practice is controversial.
Much attention has focused on an alternative solution, creating so-called induced pluripotent stem (iPS) cells by reprogramming the genes of adult cells.
However, iPS cells, made by injecting a cell with foreign genes, have a known tendency to trigger uncontrolled tumour growth.
Stap cells could potentially lift this barrier to using stem cells in medicine, though scientists are still a long way from conducting such experiments.
So far Stap cells have only been made from immature mouse cells.
Writing in Nature, Professor Austin Smith, from the Cambridge Stem Cell Institute, said: “It remains to be seen whether adult cells will respond similarly.”
Prof Mason stressed that Stap cells will not immediately replace iPS cells, just as iPS cells have not replaced ES cells.
He added: “Every breakthrough has to catch up with the years of accumulated scientific and clinical knowledge that the earlier discovery has generated. However this knowledge pool accelerates the development of later discoveries enabling game-changing technologies to progress faster to the clinic.
“For example, it took human ES cells 12 years before their first use in man but only six years for human iPS cells. Given the substantial overlap between all three technologies, it is likely that this will shorten the development pathway for Stap cells, however, it will still be many years before the technology could potentially be in everyday clinical practice.”
Leading stem cell scientist Professor Robin Lovell-Badge, from the MRC National Institute for Medical Research in London, said: ``The reprogramming induced by low pH is remarkable.
“It is going to be a while before the nature of these cells are understood, and whether they might prove to be useful for developing therapies, but the really intriguing thing to discover will be the mechanism underlying how a low pH shock triggers reprogramming. And why it does not happen when we eat lemon or vinegar or drink cola.”