Safety Improvements for Stem Cell "Taxi Cab"

A remarkable recent discovery is that adult cells from (for example) an individual’s skin can be manipulated and “reborn” as primitive stem cells, that can turn into the many different types of cells required to form a human being. Called inducible pluripotent stem cells (iPS), these cells could treat incurable degenerative diseases, even allowing doctors to replace entire organs.

Before iPS can be widely introduced into the clinic, however, they must be shown to be safe and to behave in a predictable manner. An article by Kane and others from the United Kingdom in this month’s Molecular Therapy emphasizes why we need to proceed with caution.

An ordinary adult cell can be turned into an iPS by introducing new genes that are usually only seen in primitive cell types. The cell machinery then functions as though it belongs to a stem cell, producing all the other changes necessary for adult cells to transform into iPS. These new genes, which trigger the transformation, are usually introduced using viruses that transport and drop them off into the cell’s nucleus - like a taxi cab.

Kane and others now show that even if the “taxi cab” is empty, they can still make random changes to the cell that can convert adult cells into iPS cells.

Why should this be a problem? If empty viruses can produce this effect, then it is likely that they are also causing unknown, uncontrolled and unpredictable changes to the cells’ genetic makeup, some of which might turn cells cancerous.

Investigators are now trying to turn adult cells to iPS cells without viruses or genetic manipulation, but as yet these processes are inefficient and of unknown safety. Ultimate reassurance may require inclusion of a self-destruct switch that can be triggered in harmful iPS.