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Role of Extracellular Matrix Factors in Stem Cell Differentiation Supported by Reports in Stem Cells and Development.

NEW ROCHELLE, N.Y. -- Proteins and growth factors present in the extracellular matrix can drive stem cell differentiation by regulating gene expression, a finding shared by a series of papers published in the December 2005 (Volume 14, Number 6) issue of Stem Cells and Development, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com). Several key papers in the series are available free online at www.liebertpub.com/scd.

Therapeutic applications of stem cells aimed at regenerating damaged tissues and organs will require targeted differentiation of stem cells into specific progenitor cell types and an understanding of the factors that affect stem cell differentiation. The series of papers in this issue of the Journal shed light on the role that extracellular matrix (ECM) factors play in determining the fate of human stem cells grown in culture.

"The matrix upon which the cells reside was long thought to have an influence on cellular responses," says Editor-in-Chief Denis English, Ph.D., Professor of Neurosurgery and Director of Cell Biology at the Center of Excellence for Aging and Brain Repair of the University of South Florida College of Medicine in Tampa. "Recent studies show that it not only influences cell responses, it defines them. The matrix is perhaps the key factor in the functional activity of mature cells when they coalesce to form multicellular structures during, for example, wound healing. Recent reports in Stem Cells and Development show that the matrix is also perhaps the most important factor in directing stem cell differentiation. In this process, the stem cells' response to the matrix changes the matrix. This process sets up a complex but orchestrated and predictable dynamic response that continues as development progresses," concludes English.

This issue of Stem Cells and Development features a group of reports examining the conditions that support the differentiation of stem cells grown in culture into a variety of defined cell types. In a paper entitled, "Substrate Induction of Osteogenesis form Marrow-Derived Mesenchymal Precursors," Simon Cool and colleagues from the Institute of Molecular and Cell Biology (Singapore), as well as Victor Nurcombe and associates from the National University of Singapore, conclude that ECM elements normally found in bone--such as laminin-1, fibronectin, and collagen-1--have a defining effect on the differentiation of bone marrow progenitor cells.

Robert Schwartz and colleagues from the University of Minnesota in Minneapolis studied the role of cytokines and specific ECM proteins in the differentiation of human embryonic stem cells. They demonstrate that fibroblast growth factor-4 and hepatocyte growth factor led to hepatocyte specification of the cultured stem cells in a paper entitled, "Defined Conditions for Development of Functional Hepatic Cells from Human Embryonic Stem Cells."

"Changes in the ECM have a direct impact on stem cell differentiation," writes Roman M. Salasznyk and colleagues of the laboratory of George Plopper of the esteemed Rensselaer Polytechnic Institute in Troy, NY, and the Siena College of Loudonville, NY, in their report entitled, "Focusing of Gene Expression as the Basis of Stem Cell Differentiation." The results led the authors to enhance their conclusions published in the August issue of the Journal which presented for the first time the now well-received hypothesis that differentiation of stem cells is directed by matrix clues that result from gene focusing, or the enhanced expression of functionally related clusters of proteins, rather than new gene expression.

Evidence to support the role of insulin-like growth factor-I (IGF-I) in osteogenic differentiation of human adult mesenchymal stem cells is presented by Hannjorg Koch and coworkers from the University of Greifswald (Germany), Carnegie Mellon University (Pittsburgh, PA), and the University of Pittsburgh, in the paper, "Insulin-like Growth Factor-I Induces Early Osteoblast Gene Expression in Human Mesenchymal Stem Cells." This work, led by Dr. Phil Campbell of Carnegie Mellon, is defining and consistent with the other papers in the December issue of the Journal.

The results presented in these reports lead to a new concept of the notion of stem cell plasticity, since similar changes can be effected in mature cells on diverse matrices. They also lead to a new concept of development, wherein the process is viewed as a continuous process that is orchestrated by the matrix as well as soluble factors, and the matrix is altered as the process proceeds, changing the cells' response as the response continues to a successful endpoint.

Stem Cells and Development is an authoritative peer-reviewed journal published bimonthly in print and online. The Journal is dedicated to communication and objective analysis of developments in the biology, characteristics, and therapeutic utility of stem cells, especially those of the hematopoietic system. A complete table of contents and free sample issue may be viewed online at www.liebertpub.com/scd.

Mary Ann Liebert, Inc., is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Cloning and Stem Cells, Human Gene Therapy, and Tissue Engineering. Its biotechnology trade magazine, Genetic Engineering News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 60 journals, books, and newsmagazines is available at www.liebertpub.com.
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