Genetic selection of target stem cell populations

Nov 29 2007

Human embryonic stem cells can be genetically manipulated to help select out desirable cell types, according to a University of Nottingham study published online in Molecular Therapy.

This advance could help scientists develop better ways of deriving useful cell populations for therapeutic and research purposes.

Although human embryonic stem cells (hESCs) can theoretically become any kind of cell in the body, directing this differentiation and selecting for a particular cell type is challenging.

Dr Chris Denning and his team at The University of Nottingham manipulated certain genetic targets in their stem cells to enhance the selection of heart muscle cells from other cell types present in their culture.

They increased the percentage of heart muscle cells present to as much as ninety-one percent by selecting out fast dividing cells and selecting for cells that expressed genes characteristic of these slower dividing cardiac cells.

According to the authors, this strategy could be easily manipulated to select for other cell types. This paper is one of the first to document the successful selection of one kind of cell in hESCs — an important step towards realizing their potential.

Dr Denning, of the Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM) at The University of Nottingham, said: “Human embryonic stem cells are remarkable because we can keep them at a primitive stage of development for a long time in the laboratory, and yet by changing their environment we can also coax them into becoming virtually any cell type within the human body.

“This includes beating heart cells, also known as cardiomyocytes. In the longer term, cardiomyocytes could be used for testing the safety of new pharmaceutical products or for transplanting into patients hearts after heart attack. The trouble is that these uses will require pure populations of cardiomyocytes but until now whenever we have produced cardiomyocytes, we have also produced many other unwanted 'contaminating' cell types such as brain cells or liver cells.

“What we describe in the present research is a method to eliminate the unwanted cells and produce almost pure populations of cardiomyocytes.

“There is still a lot of work to be done, but this really does provide a first step towards being able to use cardiomyocytes derived from human embryonic stem cells for important clinical applications.”