Melton

(Best Syndication News) Scientists have been able to change the function of non-insulin producing adult pancreatic cells into insulin producing beta cells using viruses to transport just three genes. Although the experiments were done on mice, the investigators are excited about the potential of the concept and its use on humans. (see videos below)

No Need For Stem Cells

The technique does not involve embryonic stem cells. The researchers were able to reprogram adult pancreatic cells using viruses as a “shuttle”. They changed the functional identity of the adult cells and the process was quick, according to their report. The method is sometimes referred to as “adult cell switching” or “lineage switching”.

Regenerative Medicine

They changed the genetic programming. The regulatory genes changed the job description of the cells instantly, and that function lasted for as long as nine months. Rather than relying on embryonic stem cells or reversing the cell’s genetic programming in the earliest stages, this technique can regenerate and change the function of adult cells.

Douglas A. Melton, a Howard Hughes Medical Institute (HHMI) investigator, and his colleagues were amazed by the speed of the process. “What this shows is that you can go directly from one type of adult cell to another, without going back to the beginning,” Melton said. “It's like turning a scientist into a lawyer without sending her all the way back to kindergarten.”

Insulin Producing Beta Cells and Type-1 Diabetes

The scientists were looking for a way to convert common exocrine cells to the relatively scarce beta cells. About 95 percent of the pancreas is composed of exocrine cells. The insulin producing beta cells are destroyed in patients with type-1 diabetes. Insulin, a hormone created by these cells, causes most of the body’s cells to absorb glucose (sugar) from the blood.

Patients with diabetes lack the insulin and the ability to transfer the glucose to the muscle and other cells. The body begins to use the fat as an energy source. This can lead to complications because there is too much sugar in the blood (hypoglycemia). Those complications include ketoacidosis, or nonketotic hyperosmolar coma, eventual cardiovascular disease, chronic renal failure, retinal damage, nerve damage and microvascular damage which may cause impotence and poor wound healing.

Previous Research

In 2006 Japanese researcher Shinya Yamanaka and his colleagues made stem cells from adult mouse skin cells (fibroblasts) by inserting four specific genes that were active in mouse embryonic stem cells. Melton wanted to incorporate this research into their experiments.

Like with the exocrine cells, the skin cells had the genes but they were just turned off. Yamanaka was able to reprogram the skin cells into pluripotent stem (iPS) cells which could develop into any type of tissue. It was hoped that these iPS cells could be used to repair damaged nerves, hearts, or other organs.

Converting Exocrine Cells Into Insulin Producing Beta Cells

The experiments of Yamanaka prompted Melton and his colleague Qiao “Joe” Zhou to wonder if they could use a similar technique to change one cell into another type of cell.

Common exocrine cells which churn out digestive enzymes are the same as Beta cells, except they have a few genes turned off. The exocrine cells have the genes needed to produce the insulin, but they are “silenced”. The goal of these experiments was to “awaken” those genes.

From a list of 1,100 transcription factors in mice, the HHMI scientists selected 200 that were active in cells from the pancreas. They narrowed that list down to 28 of the most active factors in the region of the pancreas that contains the beta cells. Finally they learned that only three of the transcription factors (Ngn3, Pdx1, and Mafa) were needed to convert the common exocrine cells into Beta cells.

The scientists used retroviruses to carry the genes. They were amazed that it only took three cells to change exocrine cells into the insulin producing cells. Although the transcription factor genes disappeared in two months after they were introduced with the virus, the converted cells remained.

Genetic Switching

Rather than creating stem cells to fix problems, this technique converts one cell directly into another. Melton's work is going to inspire an explosion of experiments in this direction. They believe they can convert other cells using this switching method.

It may be more practical to just convert the cells rather than having to reprogram them back to pluripotency,” says George Daley, a Howard Hughes Medical Institute (HHMI) investigator.

Other Research By Daley

Daley recently reported that they had converted cells from individuals with 10 degenerative diseases into stem cells with the same genetic errors. The newly created stem cells can allow researchers to reproduce human tissue formation in a Petri dish as it occurs in individuals with any of the diseases.

The new research by Melton is published in the August 27, 2008 advance online publication of the journal Nature.

By Jeffrey Workman
Best Syndication News Health Writer

Stem Cells