The Roles of Individual Growth Factors on Differentiation

Abstract

Embryonic stem (ES) cell research has a long way to go if it will someday provide us with replacement organs or tissues. One problem is not knowing what growth factors influence ES cells. Another dilemma is figuring out how to effect the differentiation of ES cells into desired differentiated cell lineages. Schuldiner et al. studied aggregates of ES cells called embryoid bodies and the effects of several growth factors on their differentiation. By analyzing the expression of various transcripts known to be markers for specific cell differentiation, the authors were able to categorize the effects of growth factor treatment into three groups: differentiation into mesodermal-like cells was induced by activin A or transforming growth factor-β; formation of cells with both mesodermal and ectodermal characteristics was induced by retinoic acid (RA), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), or bone morphogenetic protein-4 (BMP-4); and formation of cells with characteristics of mesoderm, ectoderm, and endoderm was caused by nerve growth factor (NGF) and hepatocyte growth factor (HGF). However, the application of single growth factors to ES cells did not cause full differentiation into one specific cell type. Thus, although this work represents a first attempt at determining the effects of growth factors on pluripotent cells, other variables essential for proper differentiation, including the timing and impinging of multiple growth factors onto ES cells, will have to be accounted for in future studies.Schuldiner, M., Yanuka, O., Itskovitz-Eldor, J., Melton, D.A., and Benvenisty, N. (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 97: 11307-11312.[Abstract][Full Text]