Scientists around the world are continuously working tirelessly in their search to understand the human body, along with the cancers and other devastating diseases. The goals are to discover curative therapies. Embyronic stem cell research brings the promise of understanding the development of organs, which in turn could be applied to other developmental diseases, such as cancers.

The development of a human (Fig. 1), starts after a sperm fertilizes an egg, resulting in the generation of the blastocyst. This contains a mass of cells, termed the inner cell mass, which is the source of embryonic stem cells, or pluripotent cells. The embryonic stem cells can develop into cells of all tissues to develop into a fully formed human (Fig. 1).

Figure 1.  Embryonic develpment.

The inner cell mass contains the cells that can generate cells of all germ layers: ectoderm, mesoderm, and endoderm. The ectoderm is the outer most layer which forms skin, brain, the nervous system, and other external tissues, mesoderm is the middle layer which forms muscle, the skeletal system, and the circulatory system, while the endoderm is the inner most layer of the gastrula which forms the lining of the gut and other internal organs.  In turn, the three germ layers are the precursors to all the cells that form a human.  The mere fact that the cells of the inner cell mass give rise to such a wide array of cell types forms the basis for a push with embryonic stem cells as a form of cell replacement therapy.

The source of embryonic stem cells for research have raised some religious and ethical concerns, because as mentioned earlier embryonic stem cells are obtained from the inner cell mass of a developing embryo.  Embryonic stem cells are derived from excess embryos created in the course of infertility treatment. In vitro fertilization is initiated with the fusion of an egg and sperm in the laboratory. During the process of in vitro fertilization, excess human embryos are created. It is these excess stem cells that are donated for research purposes. On August 9, 2001, the President of the USA announced that 60 embryonic stem cell lines are approved for federal-funded research. These cell lines were generated from donated embryos, and not from cloning.  What makes Embryonic Stem Cells (ESCs) unique is not only their pluripotency, since adult stem cells also show similar property, but their ability to form all types of cells. 

The ethical controversy surrounding human embryonic stem cell (ESC) research arises from the fact that in order to obtain these cells living human embryos must be disaggregated and destroyed.  In an effort to alleviate the debate and controversy over the harvesting of embryonic stem cell for use in research,  new techniques have been proposed to help in the development of new stem cell lines. To date, these techniques have been used only in mice. The first technique, referred to as altered nuclear transfer (ANT), also termed cell cloning, involves genetic modification to create “embryos” that are disabled and cannot be developed past the blastocyst stage. Thus these cells cannot be used to clone a human. Supporters for this technique argue that the inability of these embryos to continue the developmental process renders this a moral research option because it does not require the destruction of viable embryos.  

 
The second technique proposes to extract one cell from the 8-cell stage of the developing embryo (Figure above). This single cell could be cultured under the appropriate condition in the laboratory to generate embryonic stem cells. The remaining 7-cell embryo will then go on to form an adult. It should be noted that this research has only been studied with mouse models. This is not a new technique as it is identical to the method used for in vitro fertilization to screen for defective embryos. Supporters of this technique argue that this is an ethical research option because it does not involve the destruction of an embryo. These techniques have not been used in humans and the full extent and understanding of the pluripotency of the stem cell and its potential usefulness in humans has not been reported.    

Research studies with embryonic stem cells shows promise for future therapies. Despite their potential for regenerating tissues and organs, there are many obstacles that must be overcome. Ongoing and future research with embryonic stem cell is imperative, because the full understanding of the development of these stem cells might hold the key to unlocking the answers for developmental processes and/or cell therapies.

Acknowledgements

This review was prepared by the following graduate students in the Stem Cell Biology Class, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey:
Olufunke Amele, Shreya Chakravarti, Colin Craig, Michael Ricardo, Anthony Shoo (In alphabetical order)

Teaching Assistant:  Kelly Corcoran

The review was edited by two stem cell biologists.