Translational Research: Toward Better Characterization of Human Embryonic Stem Cell Lines
Version of Record online: 1 NOV 2005
Copyright © 2005 AlphaMed Press
Volume 23, Issue 10, page 1453, November 2005
How to Cite
Rao, M. S. and Civin, C. I. (2005), Translational Research: Toward Better Characterization of Human Embryonic Stem Cell Lines. STEM CELLS, 23: 1453. doi: 10.1634/stemcells.2005-ed.4
- Issue online: 2 JAN 2009
- Version of Record online: 1 NOV 2005
Current U.S. policy on human embryonic stem cell (hESC) lines is a dual-track policy. About 20 lines derived from the 70 derivations undertaken before August 9, 2001, are available (and in sufficient quantities) such that basic researchers can obtain them for research studies. Research projects using these lines are eligible for federal funding, and the bulk of research reports published have used these cell lines. Despite their overall similarity in self-renewal, expression of markers, and ability to differentiate, certain differences among these lines have also been reported. These include differences in growth rates, ability to form rosettes, gene methylation patterns, karyotypic stability, polymorphisms, and changes associated with long-term propagation in culture.
In the last few years, a host of additional hESC lines have been generated. These include cell lines derived at different stages of early embryonic development, lines derived using different methods of isolation, and lines derived from embryos carrying a known genetic defect or generated via somatic cell nuclear transfer. Although it is legal to work on these lines in the U.S., the infrastructure for large-scale characterization of stem cell lines developed over many years involving NIH and other federal support cannot currently be used to characterize these lines.
Given the numbers of new hESC lines that continue to become available, the lower cost to obtain them (free for many derived post-August 9, 2001, vs. more than $5,000 for most lines that predate that time), and their diversity and other qualitative advantages, it is likely that many of the new cell lines will be studied, perhaps by different investigators.
The Drive for Comparative Data
Stem cell investigators have realized that it will be critical to establish methods of comparing lines irrespective of their time of generation, method of isolation, and conditions of propagation to assess which lines are optimal for laboratory research or, eventually, for therapy. This has sparked numerous efforts at generating comparative data. The International Stem Cell Consortium, led by Dr. Peter Andrews (Sheffield, U.K.), has undertaken to examine the properties of 70+ hESC lines. The stem cell center at the NIH has undertaken to develop and publish standardized conditions for the growth and propagation of all the available NIH-approved pre-August 9 lines. A proposed stem cell bank is likely to use uniform culture conditions to maintain lines for U.S. federally funded studies. The American Type Culture Collection, partially funded by the National Institute on Aging but with access to additional non-Federal funds, has undertaken a detailed analysis of pre- and post-August 9, 2001, lines to ensure a common dataset of parameters, thus enabling comparisons of lines.
To help establish and disseminate a consensus and provide a forum for critically evaluated, peer-reviewed methods papers, Stem Cells has committed to publishing critical reports on standardization. In addition, we have invited the leading groups working on this critical issue to submit editorial or opinion pieces. We also invite readers to send us their responses.
In this issue, Dr. Melissa K. Carpenter (Robarts Research Institute, London, Ontario, Canada) describes how X chromosome inactivation can be assessed in ESCs; Dr. Peter Sartipy (Cellartis AB, Göteborg, Sweden) describes how quantitative real-time polymerase chain reaction can be used to rapidly assess the state of ESCs; and Dr. Bernard Lo (University of California-San Francisco, San Francisco) discusses ethical issues in hESC research, with an eye to clinical trials of transplantation. In the October issue, Dr. Heli Skottman (Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland) described gene expression signatures of seven individual hESC lines. Look for additional reports and commentary on standardization in future issues of the journal.
We note that the need for standardization of tests is equally critical for other stem cell populations as they are moved to the clinic, and Stem Cells encourages leading investigators in each subfield to consider how best to obtain a consensus. The journal remains committed to its mission of promoting the rapid dissemination of critically reviewed information that is important to the stem cell field and will work with groups to ensure that such information is critically apprised and made readily available.
Mahendra S. Rao, M.D., Ph.D.
Curt I. Civin, M.D.