Celulas Madres - Paper

Laboratory Investigation (2009) 89, 259–262
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PATHOBIOLOGY IN FOCUS

Human embryonic stem cells: 10 years on
Paul J Gokhale and Peter W Andrews*
Substantial advances in the biology of human embryonic stem (ES) cells, and the technology for working with them, have been made over the past 10 years. Regulatory frameworks for their studyare well developed, although some countries remain particularly restrictive. Markers and criteria for characterising human ES cells are also generally agreed, and protocols for promoting their differentiation are being established, providing the groundwork for the development of applications over the next 10 years. The recent appearance of technology to convert somatic cells to ’inducedPluripotent Stem Cells’ closely resembling ES cells will certainly speed up these developments.
Laboratory Investigation (2009) 89, 259–262; doi:10.1038/labinvest.2008.162; published online 19 January 2009

KEYWORDS: embryonic stem cells; pluripotent cells

This October marks the 10th anniversary of the first reported derivation of human embryonic stem (ES) cells.1 The report was met with much acclaimas it was quickly recognized that the ability of these pluripotent stem cells to differentiate into all cell types of the human body could provide a source of cells for replacing tissues lost to injury and disease—the ultimate goal of regenerative medicine. Inevitably, these early discussions overlooked the substantial hurdles that lay in the way, leading to disappointment in some quarters that,10 years later, more progress has not been made. Yet in the more mundane world of small molecule drugs, the pharmaceutical industry typically expects a delay of 10–15 years between initial discovery and delivery to market, whereas in the perhaps more pertinent case of monoclonal antibodies, first reported in 1975, it is only in the past few years, 30 years on, that significant monoclonalantibody-based treatments for cancer have appeared on the market. The great advantage of ES cells over other stem cells is that they can generate many potentially useful cell types—but that is also their disadvantage. To use ES cells effectively in regenerative medicine, or in other applications, such as disease modelling or drug discovery, applications that are often over looked in popular discussion, itis essential that we understand how to control their differentiation. This is necessary if one is to expand cultures of the undifferentiated cells to a usable scale, free of potential pathogens. It is also necessary if one is to produce specified cell types, free of other unwanted cells, and if the genetic fidelity of the cells is

to be preserved, a factor that was not immediately apparent whenthese cells were first derived. These issues present substantial challenges, but slowly they are being overcome as we begin to gain insights into the biology of these fascinating cells.
DERIVATION AND MAINTENANCE OF HUMAN ES CELLS Human ES cells are derived by disrupting early human embryos at the blastocyst stage and placing them in culture under specialized conditions.1 At this time, it isvariously estimated that over 300 such lines have been derived in many countries around the world. However, the need to destroy embryos raised many ethical and legal issues that have been addressed in different ways in different countries. The UK has been at the forefront of regulation in this area and a 1990 law specifically established the legal framework for experimental work with human embryos.This law provided for a body, the Human Fertilisation and Embryo Authority, from which any work, whether for assisted conception or research to produce ES cells, must be licensed. A separate body, the UK Stem Cell Steering Committee oversees subsequent work with human ES cell lines once established. Other countries took a wide variety of different approaches. Some completely banned work with...