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Discovery of embryonic stem cells and the concept of regenerative medicine 

Discovery of embryonic stem cells and the concept of regenerative medicine

Chapter:
Discovery of embryonic stem cells and the concept of regenerative medicine
Author(s):

Martin J. Evans

DOI:
10.1093/med/9780199204854.003.0407
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date: 30 March 2017

The differentiated cells of the adult vertebrate arise from a single fertilized egg and as development proceeds the commitment to differentiation becomes irreversible.

During early development a few cells give rise to all the differentiated tissues; these original cells are thus pluripotential.

In malignant tumours small populations of self-renewing cells may arise; these divide to generate rapidly differentiating cells and others, like themselves, which remain undifferentiated.

The original experimental observation that teratocarcinoma cells spontaneously differentiate into benign cell types, embryos, or primordial germ cells questioned the idea that the cellular differentiation was a spontaneous reversion from malignancy: perhaps stem cells within teratocarcinomas were essentially normal?

Discovery of embryonic stem cells made it possible to generate chimeras in the context of a carrier mouse embryo; the demonstration that these could contribute to the germline provided a route to genetic manipulation (transgenesis) from cells in culture to the intact adult mammal. This has been of critical importance for the generation of experimental animals that serve as authentic models of human inherited disease—with numerous technical refinements inducible and conditional models can be produced, almost at will, for study. It is moreover possible to disrupt any locus in the mouse (and now other mammalian) genome(s) in order to investigate the function of particular genes in the living animal.

Teratocarcinomas also occur in humans and their study has stimulated the developing concept of regenerative medicine—a concept further enriched by the isolation of human embryonic stem cells with differentiation properties similar to those of murine origin. In addition, knowledge about the factors that maintain pluripotency and suppress differentiation has allowed reprogramming of differentiated cells, such as skin fibroblasts, back into the embryonic stem-cell state. These scientific discoveries provide opportunities for using pluripotential cells in regenerative processes; those that are self-derived, would evade immune rejection.

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