Stem cells are unspecialised cells that have the extraordinary potential to either proliferate through mitosis to produce more stem cells or to differentiate, under certain physiological or experimental conditions, into more specialised cells such as brain or muscle cells.
There are broadly speaking two types of stem cells: embryonic stem cells and adult stem cells. Adult stem cells together with progenitor cells (stem cells that are partially differentiated) act as an injury/repair mechanism and have the ability to repopulate specific tissues whereas embryonic stem cells have the ability to differentiate into all specialised cells as well as maintaining healthy tissue. The use of human embryonic stem cells remains an ethically contentious issue due to the potential destruction of the embryo to retrieve the inner cell mass.
In recent years there have been great advances in reverting adult specialised cells back to an undifferentiated state. The methods used to create these cells involve the manipulation of various genetic factors and it takes many weeks to create a stable cell population. These cells are known as ‘induced pluripotent stem cells’ or iPSCs and in the future may become as scientifically useful as embryonic stem cells but without the ethical concerns. James Thompson, one of the principal founders of iPSCs, commented: “If you can’t tell the difference between iPS cells and embryonic cells then embryonic stem cells will turn out to be a historical anomaly.” There appears to be consensus of this opinion in the scientific community.
The use and development of human induced pluripotent stem cells (hiPSCs) has many distinct benefits to cellular and molecular human disease research (and toxicity testing) and consequently excellent animal replacement potential for many different research areas. One of the key and yet often overlooked benefits of these cells is that an almost inexhaustible supply of relevant cells types can be created for research purposes, which can help reduce the burden of sourcing clinical biopsy and human tissue samples. Even though hiPSCs have the potential to become almost any type of human cell it should be noted that not all cell types can be reliably produced as the specific conditions that are required are complex and incredibly challenging to create.
There are many impressive examples of iPSCs on YouTube. The two videos particularly worth viewing are from Cellular Dynamics International
and Shinya Yamanaka
It is astonishing to observe the synchronised beating of iPSC derived cardiomyocytes (heart cells) that were once adult skin or blood cells. These cells are incredibly useful in drug discovery programmes to aid the prediction of drug efficacy and toxicity without the use of animals.
Recently we have funded two exciting animal replacement research projects, which feature iPSCs: is currently investigating iPSCs as an acceptable replacement model for pre-clinical drug screening in haematological malignancies and Professor James Ross at the University of Edinburgh produced hiPSC-derived, functionally mature, hepatocytes for the replacement of animals in toxicology testing (more information to follow).