Stem cells with Nobel glamour

They’re lining up outside Marek Łos’ door

The discovery awarded this year’s Nobel Prize in Medicine, induced pluripotent stem cells (iPS), is good news for everyone who needs to replace an organ that’s out of order. Soon there will be a line of researchers outside the door of Marek Łos, who is fabricating iPS cells in his laboratory at Linköping University. (20 Dec, 2012)

Organ transplants became a realistic possibility in health care in the middle of the last century. The first kidneys were transplanted in the United States in 1950.The next revolution came while this century was still young. We are no longer obliged to use donated organs but can produce new ones, like the corneas recreated in ten visually impaired patients five years ago in Östergötland.

A tissue can be likened to a wall with bricks and mortar. The cells are the bricks and the matrix around them – or an artificial biomaterial – is the mortar. It’s a matter of being able to develop the right type of cells for the organ to be recreated or repaired. For that, you need stem cells.

When the hype around stem cells first broke out, human embryos were the target. They have immature cells that specialise during development into all the different cell types in the human body. Any tissue at all could be created by harvesting these cells from embryos left over from test tube fertilisation. But, problems quickly lined up.

To support the demand, permission to fabricate embryos just for that purpose was needed, which raised ethical questions. The cells would also be genetically different than those of the recipient, which requires suppressing the immune system to prevent rejection.

In the United States, the question went all the way to the White House, where President George W. Bush forbade all research on newly produced embryonic stem cells.

But now there is an alternative: iPS, or induced pluripotent stem cells. Their discovery and development was recently awarded the Nobel Prize in Physiology or Medicine.

It was shared by an elderly Englishman and a middle-aged Japanese, who showed that any body cell at all could be reversed to its origin as a stem cell.

“The beauty of iPS is that you can take the cells from the same person who is getting the new organ. So you avoid the risk of rejection. At the same time, it opens up a source for testing new drugs on laboratory-produced tissues,” says Marek Łos, professor of Regenerative Medicine and Linköping University’s leading expert in the area.

Englishman John Gurdon discovered a half-century ago that cells’ specialisation is not irreversible. When he replaced the nucleus of a frog’s egg with the nucleus from a mature, specialised cell from a frog’s intestine, the egg could still develop into a viable tadpole. The experiment showed that the specialized cell still contained all the genetic information needed to construct all kinds of frog cells.

More than 40 years later, the Japanese Shinya Yamanaka took the next important step when he discovered that it was possible to reverse the mature cell to its original state – the induced pluripotent stem cell. What was needed was production of transcription factors: proteins that control the flow of genetic information from DNA to RNA.

These can, in turn, be directed to take the shape of all the various cells that go into building the body.There are, however, certain risks with all stem cells. As far as iPS are concerned, there is a small risk that old, dormant virus particles could be activated and get into the genome.

“The Holy Grail is to find a way of avoiding all genetic material in the reprogramming, and use only proteins.”

Łos ranks Gurdon’s and Yamanaka’s discoveries among the most important of the last hundred years. Yamanaka’s share of the Nobel Prize is also one of the “fastest” – six years after the decisive publication.

Professor Łos – with a background in Poland, Germany, and Canada – is leading a research group working with iPS to produce corneal cells, skin cells, and cardiac muscle cells for ongoing projects in regenerative medicine.

Reprogramming connective tissue cells takes three to four weeks. Only one out of every 200 cells manages to reach the goal of becoming an iPS. After that, special conditions and growth factors are needed to turn development anew in the direction of the desired cell type.

“The next big step will be to develop effective production, maybe with the help of proteins or nanoparticles,” Łos says.

Text: Åke Hjelm
Picture 1: Marek Łos surrounded by his research group. From the left: Wiem Chaabane, doctoral student from Tunisia, Jaganmohan Reddy Jangamreddy, doctoral student from India, Mayur Vilas Jain, doctoral student from India, Artur Cieślar-Pobuda, postdoc from Poland, and Caspar Bundgaard Nielsen, master’s student from Denmark. Photo: Vibeke Mathiesen
Picture 2: Marek Łos and Artur Cieślar-Pobuda freeze cell cultures in liquid nitrogen. Photo: Vibeke Mathiesen
Picture 3: John Gurdon, Nobel Prize winner. Photo: The Nobel Foundation.
Picture 4: Shinya Yamanaka, Nobel Prize winner. Photo: The Nobel Foundation.

LiU Magazine 4-2012
20 Dec, 2012