Scientists create reprogrammable mouse in stem cell breakthrough, opening a new way to regenerate failing tissues in patients with diseases ranging from heart failure to diabetes

September 11, 2013 6:04 pm

Scientists create reprogrammable mouse in stem cell breakthrough

By Clive Cookson, Science Editor

Scientists in Spain have produced the world’s first embryonic stem cells within a live animal rather than in a laboratory dish. The experiment with mice at the National Cancer Research Centre in Madrid could open a new way to regenerate failing tissues in patients with diseases ranging from heart failure to diabetes. Therapeutic applications – for example to repair damaged spinal cord or make new insulin-producing cells – are distant. Even on the most optimistic assumptions clinical trials in people are unlikely to start in less in than five years, according to Dr Serrano.Therapy might involve inserting the reprogramming genes into a harmless virus that would carry them into diseased or damaged human tissues, where they would produce first stem cells and then rejuvenating specialist cells.

The researchers in Madrid adapted the technique for which Shinya Yamanaka of Japan won a Nobel Prizelast year. The Japanese team created embryonic stem cells of a new type – induced pluripotent stem cells or iPSCs – by reprogramming adult cells in a lab dish with a combination of four genes, which turned their clock back to an immature stage where they can become any sort of specialist cell.

The Spanish group bred genetically engineered mice with the same cocktail of four reprogramming genes – and switched them on by adding a particular drug to the animals’ drinking water.

After a few weeks, embryonic stem cells had appeared in multiple tissues and organs. The researchers extracted these cells and demonstrated through various tests that they were like those in a new embryo containing just 16 cells. This is an even earlier state of development than iPSCs made in vitro.

Embryonic cells made in “reprogrammable mice” also survive outside the animals in culture dishes. “So we can manipulate them in a laboratory,” said Maria Abad, lead author of a paper describing the discovery in the journal Nature. “The next step is studying if these new stem cells are capable of efficiently generating different tissues such as that of the pancreas, liver or kidney.”

“We can now start to think about methods for inducing regeneration locally and in a transitory manner for a particular damaged tissue,” added Manuel Serrano, head of the Madrid laboratory.

Writing a commentary in Nature, stem cell researchers George Daley and Alejandro De Los Angeles of Harvard University hailed the paper as “a landmark for what could become a powerful strategy in regenerative medicine: tissue reprogramming in situ”.

“The major challenge will be tightly controlling every step in this potential approach to treating patients in order to deliver clinical benefits, while avoiding potential complications,” said Chris Mason, professor of regenerative medicine at University College London. Ensuring safety will be a priority for clinical research based on the discovery, agreed Dr Serrano.