The other pages describe:
- the properties and potential therapeutic applications of embryonic (and other types of) stem cells
- how mouse embryonic stem cells can be used to make transgenic mice
- how the fusion of a differentiated cell from an adult sheep with an enucleated sheep egg can produce a clone of the cell donor ("Dolly")
The techniques used in the early steps of each process have been achieved with human cells.
Thirteen years ago a research team led by James Thomson of the University of Wisconsin reported (in the 6 November 1998 issue of Science) that they were able to grow human embryonic stem (ES) cells in culture.
At the time of implantation, the mammalian embryo is a blastocyst. It consists of the
- trophoblast — a hollow sphere of cells that will go on to implant in the uterus and develop into the placenta and umbilical cord.
- inner cell mass (ICM) that will develop into the baby as well as the extraembryonic amnion and yolk sac.
Figure 14.8.1 Blastocyst
The cells of the inner cell mass are considered pluripotent; that is, each is capable of producing descendants representing all of the hundreds of differentiated cell types in the newborn baby, including
- ectodermal cells like neurons and skin (epithelial cells)
- mesodermal cells like striated muscle, smooth muscle, cartilage, and bone
- endodermal cells like the liver and the lining of the intestine
- Remove the trophoblast cells from a human blastocyst (these were extras not needed for assisted reproductive technology).
- Separate the cells of the inner cell mass and culture them on a plate of "feeder" cells (mouse fibroblasts were used).
- Isolate single cells and grow them as clones.
- Test the clones.
- Each successful clone maintained a normal human karyotype (unlike most cultured human cells — HeLa cells, for example).
- These cells had high levels of the enzyme telomerase, which maintains normal chromosome length and is characteristic of cells with unlimited potential to divide ("immortal").
- When injected into SCID mice, these cells formed teratomas; tumors containing a mix of differentiated human cell types, including cells characteristic of
SCID = severe combined immunodeficiency.
SCID mice lack a functioning immune system (have neither T cells nor B cells) and so cannot reject foreign tissue. Some rare inherited diseases of humans are also called SCID. They produce a similar phenotype but involve different molecular defects.
Human embryonic stem cells have the potential to
- teach us about the process of human embryonic development, its genetic control, etc.
- provide a source of replacement cells to repair damaged human tissue. As the proper signals are discovered, it will be possible to cause these cells to differentiate along a particular pathway, e.g., to form insulin-secreting beta cells of the islets of Langerhans. Such cells might be able to replace lost or non-functioning cells in a human patient (e.g., with Type 1 diabetes mellitus).
However, there are problems that remain to be solved before this hope can be realized.
- Production of human ES cells requires the destruction of the blastocyst, and this is morally-repugnant to many people.
- Cell replacement therapy had better be "patient-specific"; that is, the donated cells should be genetically identical to the recipient. Otherwise, the replaced cells are at risk of being rejected by the host's immune system. [Link to a discussion of "therapeutic cloning" — a method to avoid this.
- ES cells are pluripotent and might differentiate in unwanted ways when introduced into the patient.