Stem-cell research gets new horizon

Stem cell therapy involves inducing stem cells to turn into healthy new tissue to replace failing tissue

WHEN JAMES THOMSON of the University of Wisconsin-Madison demonstrated in 1998 how to prepare human embryonic stem cells, it seemed to herald an exciting new era in medical research. Unfortunately progress since then has been painfully slow and no new cures have been found.

In addition, many people object on ethical grounds to human embryonic stem-cell research because harvesting the cells entails killing embryos. Now, however, a promising new approach to curing disease using stem cells is in development, this time using the newly discovered induced pluripotent stem cells (IPSC) to develop effective new drugs. This new approach is described by Stephen Hall in March's Scientific American.

Stem cells are primordial type cells, undifferentiated themselves but having the capacity to turn into other cell types in the body. There are three types of stem cell: adult, embryonic and IPSCs.

Embryonic stem cells are the most versatile, having the capacity to turn into any of about 200 different types of human tissue cells. Adult stem cells are found in many human tissues, but have the capacity to turn into a limited number of other tissue type cells. IPSCs, discovered by Shinya Yamaka’s group at Kyoto University in 2006, are embryonic-like stem cells produced by artificially reprogramming ordinary adult cells in the laboratory. They can, in turn, be induced to turn into many tissue-type cells.

Stem cell therapy involves inducing stem cells to turn into healthy new tissue to replace failing tissue in human disease. Adult stem cells are more easily controlled than embryonic ones and established adult stem cell therapies have been developed. To date, however, no therapies have resulted from embryonic or IPSC research.

The new approach described by Hall is to use IPSCs, not directly for stem cell therapy, but to recreate various human diseases in a laboratory dish and to use these “disease in a dish” models to quickly test the effectiveness of large numbers of potential drugs against the diseases.

Until recently, such an approach relied on conventional embryonic stem cells but this method is technically difficult and ethically problematic.

The IPSC approach is easier and ethically neutral. The big pharmaceutical corporations and the biotechnology sector, which had been shying away from large investment in conventional embryonic stem cell therapy research because of slow progress, are now starting to invest in this new IPSC approach.

Hall describes how the IPSC approach is being used to find a drug to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, a slowly paralysing degenerative nerve disorder caused by the death of motor neuron cells, which control the contraction of muscles, in the central nervous system.

A small patch of skin is taken from the patient and the cells are reprogrammed in the laboratory into IPSCs. These are then chemically induced to develop into motor neuron cells, which contain the same defect that caused the disease in the patient.

So now there is nerve tissue growing in a Petri dish that exhibits the characteristics of the disease. Trays that have tissue growing in many separate wells are prepared for robotic drug screening. A single potential drug is tested per well, allowing a quick broad sweep of a wide variety of potential drugs.

Using the approach described above, researchers are now screening drugs that could enhance the survival of motor neurons. About 20 chemicals have been identified that have a positive effect in this regard and one of these drugs is now being tested in an animal model of spinal muscular atrophy.

This new IPSC approach is now in use experimentally to model dozens of illnesses, including many blood disorders such as sickle-cell anaemia and Parkinson’s disease. German researchers have created cardiac cells that beat irregularly, thereby mimicking various heart conditions.

So let us hope that at last we are on a real threshold of discovery of many new drugs that will cure or control the host of diseases that cause so much human misery.

Professor William Reville is a member of staff of the biochemistry department, UCC, and is also the university public awareness of science officer, understandingscience.ucc.ie