UNDER THE MICROSCOPE:STEM-CELL RESEARCH, currently the hottest topic in biology, is developing at lightening speed. The latest branch of this research was born in 2006 when Shinya Yamanaka of Kyoto University demonstrated a technique that turns ordinary body cells into cells that closely resemble embryonic stem cells.
The products of the new technique are called induced pluripotent stem (iPS) cells. Since Yamanaka's breakthrough, milestone publications have appeared, developing the iPS cell technique and demonstrating its potential for medical therapy. A summary of developments by Monya Baker appeared in Natureon April 23rd.
The basic unit of biological organisation is the cell. Our bodies are made of tissues and organs, each built of differentiated cells, eg liver, kidney, muscle and so on. We began life as tiny embryos made of undifferentiated cells called embryonic stem cells. These cells are pluripotent, ie have the capacity to develop into the over 200 types of differentiated cells found in the adult body. Adult tissues also contain stem cells whose developmental plasticity is less than embryonic stem cells – they are multipotent, able to develop into the differentiated cell types of their parent tissue if it suffers trauma.
Humans are prone to degenerative diseases, eg Parkinson’s and Alzheimer’s disease, muscular dystrophy and so on, where cells fail in large numbers. Stem cells hold out the prospect of curing these conditions by replacing the failed cells with new healthy cells. Prior to 2006, the stem-cell options were human embryonic stem cells (embryonic cells) and adult stem cells (adult cells) and it was argued that, over the longer term, embryonic cells were the best option because of their pluripotent nature. However, there is an ethical problem associated with embryonic cells because obtaining them entails the destruction of human embryos. Development of medical applications of embryonic cell research has also been slow and the first clinical trials using them only began in 2008. All medical stem-cell treatments to date are adult cell treatments. iPS cell technology now offers a third option, free of ethical baggage and promising to be just as useful medically as embryonic cell applications.
In 2006 Yamanaka genetically reprogrammed mouse fibroblast cells into iPS cells by incorporating into the fibroblast chromosomes 4 genes expressed in embryonic stem cells. One of the genes, c-Myc, is a cancer promoting gene but subsequent work showed how to make iPS cells without using c-Myc. Just last month research was published showing how to remove the reprogramming genes after they have produced the iPS cells and another paper showed how to make iPS cells without requiring any genetic insertion into host cell chromosomes at all. The aim is to produce iPS cells that are safe for human therapies.
Baker reports in Nature: “When it comes to studying and treating human disease, iPS cells are potentially far more useful than embryonic cells.” One immediate possibility is to use iPS cells to study disease in a laboratory petri-dish when it is not possible to get enough tissue from a biopsy (eg from brain) to study the development of the disease. iPS cells from the patient could be induced to develop into brain tissue in the laboratory and used to study how the disease begins, progresses and responds to drugs.
iPS cells also offer the possibility eventually of taking cells from a patient’s body, treating them and returning them as therapeutic cells without risk of immunological rejection. This has already been demonstrated in animals. iPS cells were made from a mouse with sickle cell anaemia and the defective sickle cell gene was replaced in these cells by a normal gene. The treated iPS cells were differentiated into blood line cells and these cells were used successfully to treat the sickle cell mouse.
Mouse embryonic stem cells were first prepared in 1981 and it took 17 years to the isolation of their human counterpart. The equivalent transition took less than 6 months for iPS cells. Stem-cell researchers have yet to make patient-matched human embryonic stem cells, but this has been already done with iPS cells made from patients with diabetes, Huntington’s disease and muscular dystrophy, Baker reports. The next goals are to make iPS cells that represent a wider variety of diseases and to develop safer and more efficient ways of making them. Yamanaka expects that potential iPS cell cures for human diseases will be in clinical trial within 10 years.
The iPS cell field is easier to get into for researchers than the embryonic cell field because the technology is simpler and cheaper, you don’t need access to human embryos and you avoid ethical problems. iPS cell research would seem to be an ideal area for Irish research to specialise in, nicely complementing the excellent existing work here on adult stem cells.
* William Reville is associate professor of biochemistry and public awareness of science officer at UCC – http://understandingscience.ucc.ie
