Embryonic Stem Cells

A Brief Introduction to Embryonic Stem Cells

Over time, this space will explore/summarize research in the area of the embryonic stem cell (ESC). This first piece is a brief introduction to this topic and highlights the areas of active research.

ESCs are derived from the inner cell mass (ICM) of the mammalian blastocyst. Similar to the ICM cells, ESCs are undifferentiated and are capable of giving rise to all cell types of the future animal and thus hold great promise for cell therapies to cure human diseases. ESCs were first derived from the mouse in 1981 (Evans and Kaufman, 1981; Martin, 1981); the first human ESC (hESC) lines were derived in 1998 (Thomson et al., 1998). Outside of their potential clinical applications, hESCs provide an extremely useful resource to investigate early human development, prior to their derivation research models for this period of human development were virtual non-existent. hESCs (or derivatives thereof) have yet to be used in any human clinical application as there is still much to be understood about the underlying biology. Areas of hESC research/discussion include:

New Derivations - This refers to the derivation of new hESC lines from human blastocysts. There are a number of reasons to derive new cell lines such as 1) to obtain hESCs uncontaminated by products derived from other animals, 2) to generate a large enough hESC bank to provide suitable allogenic diversity, 3) to derive hESCs from blastocysts obtained through somatic cell nuclear transfer, and 4) to derive hESCs from blastocysts known to carry the alleles for specific genetic diseases, this to allow research into understanding these respective diseases.

hESC Maintenance - Little is understood about the molecular signals required to maintain hESCs in the undifferentiated state. Under present culture conditions there remain a significant number of differentiated cells and these culture conditions require the presence of feeder layers to produce as yet to be defined growth factors and cytokines. Prior to any hESC-derived clinical cell therapies the hESC culture media must be fully defined.

Differentiation - The great clinical potential of hESCs is in their apparent ability to give rise to all cell types in the adult and therefore provides the potential for cell replacement therapies to treat human diseases. An example of this would be the derivation of pancreatic cells from hESCs which could then be introduced into a diabetic patient to allow synthesis of insulin and maintenance of glucose levels. The ideal situation would be to direct the differentiation of hESCs to the desired cell type, with no other cell types present, and introduce these into the respective patient. hESCs spontaneously differentiate into hundreds of different cell types. Much of the present hESC research is directed towards understanding these differentiation pathways so as to achieve a pure differentiated cell type of interest, or at least an enrichment of this cell type.

Somatic Cell Nuclear Transfer (SCNT) - The ultimate goal of this methodology (also referred to as therapeutic cloning) is to treat patients via ES cell therapies using cells that are genetically identical to the patient and thus avoid any problems with immune rejection. Theoretically, this is achieved by obtaining a nucleus from an accessible cell type of the patient in question (eg. skin cell) and placing this into an enucleated donor oocyte. This oocyte is subsequently grown to the blastocyst stage of development, a hESC cell line is derived from this blastocyst, and these hESCs are then used to generate the cell type of interest for cell therapy.

Ethical Considerations - This is an active area of discussion as hESCs are derived from a ball of cells (a blastocyst) that could potentially generate a living human being (some consider the blastocyst to already be a human being). It is important to establish/follow clear government-approved guidelines for hESC research. It is also just as important to keep the public informed and aware as to what these guidelines are and to what the current research involves.

References

1. Evans, M. J. and Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-6.
2. Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78, 7634-8.
3. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-7.