Embryonic Stem Cells: Discovery, Development, and Current Trends

Abstract

Murine embryonic stem cells were first derived almost 30 years ago from cultured blastocysts and have been primarily used as a tool to better understand development through targeted gene deletions. Only recently has the focus has shifted toward embryonic stem cells themselves and the molecular mechanisms by which they choose a specific cell fate. Through rapid advances in cell culture and genomic modification techniques researchers are beginning to regularly utilize embryonic stem cells for in vitro gene function assays. More important, the mechanisms critical for establishing the pluripotent sate of embryonic stem cells have been elucidated to the point that clinically beneficial stem cell-like counterparts can now be generated from nonembryonic sources. Keywords 1 Embryonic Stem Cells HistoryThe events that lead to the research resulting in the isolation of the first mouse and human embryonic stem cells began in 1953 at the Jackson Laboratory in Bar Harbor, Maine. This initial research was performed by Leroy Stevens, who was funded by a tobacco company determined to prove that the harmfulness of cigarettes stemmed from the wrapping paper and not the tobacco. Stevens observed that male mice of the 129Sv strain would consistently develop teratomas of the testis [63]. Over the course of almost two decades, Stevens' work showed that cells giving rise to teratomas were even present as early as the blastocyst stage, within the inner cell mass [128]. From that observation, the term "embryonic stem cell" was coined. Teratomas were subsequently used to derive cell lines with the ability to differentiate into several cell types [80]. However, because these cell lines had abnormal properties (e.g., abnormal ploidy) and retained the ability to generate teratomas, they were named "embryonic carcinoma" cells. Steven's groundbreaking discovery that pluripotent stem cells existed in early embryos resulted in multiple laboratories determining the proper culture conditions that would allow the propagation of mouse [33, 7 ] embryonic stem (ES) cells.From the onset of culturing murine ES cells, it became apparent that having the technology to introduce heritable genetic changes in the germline would be a powerful asset to studying development and disease in the mouse. Because of that fact, the focus of embryonic stem cell research in the 1980s was not the basic biology of stem cells; instead, the greatest achievement of the ES cell field at that time was considered to be the advent of gene targeting and germline modification [26, 2]. Research conducted along these lines by Mario Capecchi, Martin Evans, and Medicine.A massive resurgence of interest in the properties of ES cells took place in the late 1990s after the efforts of John Hearn's laboratory resulted first in the isolation of ES cells from rhesus monkey and marmoset ([ 5], Table 1) and subsequently to the derivation of human ES (hES) cell lines [ 3].Surprisingly, even though mouse ES cells were first isolated in 1981, rat ES proved to be much more difficult to...

Elucidating the immunohistochemistry of Nanog

“…The exact mechanisms controlling stemness have not been determined, but the research has revealed key extracellular and intracellular players. [ 20 ]…”