Abstract

Stem cell biology started with the analysis of somatic stem cells that function to maintain the adult body. We now know that the body is maintained by regeneration of a wide range of cell types, such as skin cells, blood cells and gastrointestinal mucous cells, from somatic stem cells. This regenerative activity is essential for survival. Regenerative medicine was initiated to identify therapies that support and/or accelerate this natural regenerative ability. For example, bone marrow transplantation is a therapy for reconstituting hematopoiesis from the hematopoietic stem cells present in the donor bone marrow. The successful development of a protocol for obtaining human embryonic stem (ES) cells prompted medical scientists to utilize human ES cells for regenerative medicine. However, use of these cells raises ethical issues as they are derived from human embryos. An alternative approach using ES-like pluripotent stem cells has the considerable advantage that it does not necessitate use of human embryos. Pluripotent stem cells can be induced from terminally differentiated somatic cells by the introduction of only four defined factors. The products of this method are termed "induced pluripotent stem (iPS)" cells. iPS cells have considerable promise as a substitute for ES cells not only for regenerative medicine but also in many other fields. For example, liver and heart cells derived from iPS cells can be used in pharmaceutical research. In addition, iPS cell technology opens new avenues of disease research, for example, by construction of so-called "disease-specific iPS cells" from a patient's somatic cells.

Highlights

  • This experiment famously resulted be treated with nuclear-transferred embryonic stem (ES) cells in the birth of the first live cloned sheep, produced using their own somatic cells, which named “Dolly”

  • One approach has been to search for factors in unfertilized eggs that may s be required for the reprogramming of b transferred somatic nuclei

  • Cells derived from ES or induced pluripotent stem (iPS) cell cultures have applications in many fields of medical science

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Summary

Discovery of plasticity in terminally differentiated cells

The methodology for isolating and culturing mouse embryonic stem (ES) cells was first developed in 19813 and has aided research in a wide range of biological studies. As a result of these technical advances, functional analysis of genes has progressed considerably using mice with gene knock-outs or other genetic modifications It was believed for a long time that epigenetic modifications in differentiated somatic cells m were irreversible. Following transfer of a somatic cell R m nucleus, the egg could undergo cell division S and differentiate to produce an adult frog. This J te result clearly indicated that epigenetic s modifications in terminally differentiated b somatic cells were reversible. In 1998, 17 years after the first establishment of mouse ES cell lines, it was reported that human ES cell lines could be produced by continuous in vitro culture[4]

Therapeutic cloning
Immortalization of embryonic stem cells
Clinical grade stem cells
Establishment of progenitor cell lines from iPS cells
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