The late 1960s and early 1970s ushered in the first era of stem cell research. The first stem cells to be recognized in differentiated tissues were in teratocarcinomas, a cancerous tumour. The teratocaricomas were isolated from rats, and found to contain “embryonic carcinoma” cells. These cells were noted to respond to stimulation by differentiation both in vitro and in vivo (Stevens, 1967).
Inserting these embryonic carcinoma cells into other sites in the mice caused either teratomas or teratocarcinomas in those areas of transplantation (Evans, 1972).
The embryonic carcinomas cells retained their ability for differentiation. Also, the cells could play a part in embryonic development, producing chimeras when implanted into embryos (Mintz, 1975). However the cells also lacked some fundamental characteristics of stem cells: they had alterations of their chromosomes (Papaioannou, 1975), decreased their differentiation ability over time, and otherwise lost their pluripotent capacity. The cells from these teratocarcinomas were thus confirmed as cell lines (Kahan, 1970; Jakob, 1973), but not as bona fide stem cells.
However, the behavior of these embryonic carcinoma cells was similar enough to embryonic stem cells that they were used as a model to derive similar cells from actual embryos.
The 1980s heralded the first embryonic stem cells, which were isolated from mice (Evans, 1981).
Whereas the earlier teratocarcinoma-derived embryonic carcinoma cells lost their ability to differentiate over time, the embryonic stem cells continued to maintain differentiation. When introduced into blastocysts, the resulting chimeras could contribute to all of the cell lines (Bradley, 1984).
The 1980s also saw the advances in research into the ability of the stem cells to become end somatic tissues. The cells were cultured to tissues ranging from neural to skeletal to cardiac (Wobus, 1984, Doetschman, 1985).
The next step was isolation of stem cells from humans. This was first performed using embryos collected from patients enrolled in an in vitro fertilization (IVF) program, who volunteered some embryos for stem cell research (Bongso, 1994). The embryos were cultured to produce blastocysts. The inner cell mass (ICM) of each blastocyst was separated into individual stem cells.
These isolated individual cells displayed the necessary requirements of being bona-fide stem cells (Bongso, 1994; Thomson, 1998).
Originally, stem cells were grown on animal mediums such as murine embryonic fibroblasts. However, there is an inherent risk to using such growth media in a therapeutic scenario, since could one could theoretically pass diseases from animal to the human one is trying to treat.
Therefore, an important advance culturing the human embryonic stem cells on a human-only feeder growth medium. This medium was human fetal muscle feeder in which the muscle cells were treated with mitomycin-C (Richards, 2002). These allowed human-only stem-cell preparations that avoided the so-called “xeno-contamination” from animals.
We are now in the golden age of stem cell research, in which all the technologies are assembling for actual use of stem cells.
Both therapeutic and non-therapeutic uses are exploding, which are detailed in later sections.