Pancreatic Cells To Insulin Producing Cells – The Reprogrammed Transformation

Discovering what would soon be known as the ‘third route’ to cell reprogramming, the US scientists have discovered a way by which they were able to transform living pancreatic cells in mice into another type of cell that produces insulindefine. The main point here is, that all this was done without having to revert to the stem cell stage.

The already existing technologies of stem cell reprogramming are - iPS (induced pluripotent stem cells) and hES (human embryonic stem cells). But this research would prove to be a turning point in stem cell research as it would open the gateway of possibilities to ultimately, perform living cell transformations directly in patients.

The study which was published as an advanced online paper in Nature, on 27th Augus,t was the classic work of Harvard Stem Cell Institute co-director Doug Melton and post doctoral fellow Qiao "Joe" Zhou, at Harvard University, Boston, Massachusetts, and colleagues.

The research which was done on mice involved the direct reprogramming of exocrine cells from the pancreatic tissue, into the rare beta cells, which are the pump houses of insulindefine.

While the exocrine cells account for 95 percent of the pancreatic tissue, the beta cells comprise only 1 percent of this tissue.

It should be noted that it is these very rare and precious beta cells which die in type one diabetes, thus, indicating how important the findings of this research are from the point of view of developing treatments in the future for diseases like- Type 1 and Type 2 diabetesdefine.

However, there is still time before this could become a reality, as the research has currently been done on mice and human testing of the method still remains to be done.

It has also been pointed out by the researchers that this method of direct reprogramming does not in any way eradicate the need of the already existing methods of iPS and hES.

"We need to attack problems from multiple angles," said Melton.

With two years of hard work and a sure amount of good luck, the researchers managed to hit on the three vital transcription factors required to to turn a cell into a beta cell. These transcription factors were - Ngn3, Pdx1, and MafA.

"If you want to do reprogramming it doesn't take great insight to figure out that the key genesdefine are transcription factors - the proteins that bind DNA and tell cells which genes to turn on and which to turn off.” said Melton.

In order to become a particular kind of adult cell, a stem cell passes through various stages. Each stage has a unique factor called the transcription factor. The research team in this study was looking for the factors present in the beta cells.

When they began the research, from the exocrine cells from the pancreatic tissue they had with them 1100 transcription factors. It was later found that only 200 out of these were expressed in adult pancreatic cells, it was later slimmed down a 28 factors expressed in pancreatic cells surrounding the beta cells. When the lineage studies were performed these 28 got short listed to only 9.

The team injected all of these 9 factors into the pancreasdefine and then kept removing them one by one to finally zero in on the three best transcription factors.

The conclusion of the research states that:

"This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state."