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      From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research.

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      Publication date:
      Journal: Nature reviews. Genetics
      Keywords: Animals, Embryo Research, history, Embryo, Mammalian, cytology, History, 20th Century, History, 21st Century, Humans, Male, Mice, Stem Cells, physiology, Teratocarcinoma, Testicular Neoplasms

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          Abstract

          We are currently facing an unprecedented level of public interest in research on embryonic stem cells, an area of biomedical research that until recently was small, highly specialized and of limited interest to anyone but experts in the field. Real and imagined possibilities for the treatment of degenerative and other diseases are of special interest to our rapidly ageing population; real and imagined associations of stem cells to cloning, embryos and reproduction stir deeply held beliefs and prejudices. The conjunction of these factors could explain the recent sudden interest in embryonic stem cells but we ought to remember that this research has a long and convoluted history, and that the findings described today in the scientific and popular press are firmly grounded in research that has been going on for several decades. Here I briefly recapitulate this fascinating history.

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          Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.

          G Martin (1981)
          This report describes the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice. The pluripotency of these embryonic stem cells was demonstrated conclusively by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types. Such embryonic stem cells were isolated from inner cell masses of late blastocysts cultured in medium conditioned by an established teratocarcinoma stem cell line. This suggests that such conditioned medium might contain a growth factor that stimulates the proliferation or inhibits the differentiation of normal pluripotent embryonic cells, or both. This method of obtaining embryonic stem cells makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes. The availability of such cell lines should made possible new approaches to the study of early mammalian development.
          Article 0 comments Cited 714 times – based on 0 reviews     Review now
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            Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells.

            R. L. Williams, D. Hilton, S. Pease … (1988)
            Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.
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              Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides.

              A Smith, J K Heath, D Donaldson … (1988)
              Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals and a useful system for the identification of polypeptide factors controlling differentiation processes in early development. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cells in vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA. Here, we report that purified DIA is related in structure and function to the recently identified hematopoietic regulatory factors human interleukin for DA cells and leukaemia inhibitory factor. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and hematopoietic stem cell systems.
              Article 0 comments Cited 291 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                PubMed ID:: 16534514
                DOI:: 10.1038/nrg1827

                ScienceOpen disciplines: Chemistry
                Keywords: Animals,Embryo Research,history,Embryo, Mammalian,cytology,History, 20th Century,History, 21st Century,Humans,Male,Mice,Stem Cells,physiology,Teratocarcinoma,Testicular Neoplasms
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                ScienceOpen disciplines: Chemistry
                Keywords: Animals, Embryo Research, history, Embryo, Mammalian, cytology, History, 20th Century, History, 21st Century, Humans, Male, Mice, Stem Cells, physiology, Teratocarcinoma, Testicular Neoplasms

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