Stem Cells
Vol. 25 No.
1
January 2007, pp.
1
doi:10.1634/stemcells.2006-0792; www.StemCells.com
© 2007 AlphaMed Press
OPEN ACCESS ARTICLE
STEM CELLS: A Quarter Century of Progress
Correspondence: Lawrence A. Solberg, Jr., Ph.D., M.D., Division of Hematology/Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA; Telephone: 904-953-2000; Fax: 410-953-7211; e-mail: solberg.lawrence{at}mayo.edu
Received December 6, 2006;
accepted for publication December 6, 2006.
Twenty-five years ago, most hematologists understood the concept of stem cells through the pioneering work of Till and McCullough, who created assays for the properties of self-renewal and the emergence of cells of different lineage fates from single cells marked by nonlethal cytogenetic changes induced by low-dose irradiation. Clinical use of stem cells—the collection of bone marrow cells including by sheer volume the desired subcomponent of pluripotent stem cells—and the use of this product to reconstitute hematopoiesis in patients undergoing ablative stem cell transplantation were in their infancy.
Looking back over all the articles published in STEM CELLS during the past 25 years, one can see clearly the major streams of progress. The ever more powerful isolation and enrichment for populations of embryonic or adult stem cells and the extension to cancer stem cells have been critical achievements. A novel method of stem cell enrichment has emerged through the development of zebrafish (Danio rerio) and the nematode (Caenorhabditis elegans) models with their markedly limited total number of cells undergoing self-renewal and cell fate determinations. Perhaps the primary current of change has been the slow, steady identification of the transcriptional factors and the genetic regulatory networks operating in various stem cells and stem cell niches. The molecular bases for concepts such as "plasticity" and "stemness," if not yet completely understood, are now coming into focus.
Little could one foresee that the avalanche of stem cell science into the ocean of our societies would create a worldwide tsunami in the ethical, legal, and professional domains of our lives. Witness the national controversy in the United States over the generation and use of embryonic stem cell lines and the discovery of high-profile scientific fraud. But think also of the worldwide migration of scientists to research-friendly destinations, such as Biopolis in Singapore. The recruitment of distinguished stem-cell scientists from around the world has now become a very active professional niche for talent scouts!
We fervently hope these streams of basic investigation will lead to significant progress in clinical medicine. The expansion of preclinical and clinical uses of stem cells is certainly one of the most exciting trends to develop in the past 5 years. Examples include the ongoing clinical studies for the use of stem cells in treating myocardial infarction; the deep interest in their use to treat diabetes, spinal cord injury, and neurodegenerative disorders such as Parkinson's disease; and the regeneration in vitro of tissues for use in wound repair or organ transplantation.
The advent of clinical trials, primarily in the treatment of hematopoietic disorders, has brought increasing regulation. In the United States, the Food and Drug Administration has jurisdiction over the production and marketing of any stem-cell-based therapy involving the use of human cells and patients. There are well-founded concerns: Does a donor transmit a risk for disease to a recipient? Does cell processing introduce a risk due to contamination or damage to the cells? What types of cells are present and what are their purity and potency? Will the product be safe and effective?
Biological research, including that of stem cells, is now creating an explosion of high-dimensional data. A challenge for the 21st century will be to develop and integrate mathematical and computational objects to help the human mind grasp the complexity of these systems. Two of the most fundamental needs will be for abstraction and representation. When we dash into a subway station in New York City and need to learn quickly how to get to Times Square, we have a beautiful map to use. Fortunately, all the unnecessary parts of the extremely complex subway system—the flow of employees, the electrical wiring diagrams, the engineering characteristics of the ventilation system, the flow of funds and people to support and operate the subway system—have been abstracted away by the creators of the map. And the representation is truly a beautiful and simple graph, reduced to a reasonable size on the wall of the subway.
Where is the map of the molecular regulatory states that unfold as a biological system creates an erythrocyte or a megakaryocyte from a zygote? Can one look at the genetic code of a zygote and see represented there that, 20 years hence after an automobile accident, receptors in the kidneys will sense deprivation of oxygen, increase erythropoietin production, and increase erythropoiesis?
From my viewpoint, there are two central properties of stem cells: the potential of the stem cells to produce with the utmost reliability through space and time a cardinal number of descendant cells, and a finite number of cell lineages. I think a parallel can be made to the journal STEM CELLS. The Founding Editors, Donald Metcalf, Fumimaro Takaku, Laszlo G. Latha, and Martin J. Murphy, Jr., with the strong sustaining hand of the publisher and president of AlphaMed Press, Ann Murphy, started a process that has been truly and reliably sustained through 25 years of space and time. The cardinal numbers are impressive: 1,444 peer-reviewed articles and 301 concise reviews have now been published. These articles now reach over 140,000 weekly online readers (see Figure 1) in 95 countries! On behalf of so many of us who have appreciated this journal, I extend thanks also to those who have served on the editorial board and as reviewers of manuscripts. Without them, the whole enterprise would have stopped long before reaching this station. I look forward to reading my issues of STEM CELLS 25 years from now when I am 87 years of age—perhaps supported by the very by-products of this research!
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Figure 1. Weekly online STEM CELLS readership from January 1, 2003. Peak in 2005 readership coincided with passage of California's Proposition 71, a stem cells initiative.
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Lawrence A. Solberg, Jr., Ph.D., M.D., Professor of Medicine
