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The growth of eukaryotic cells is modulated by various influences, of which growth factors are amongst the most important for many cell types. A wide range of polypeptide growth factors have been identified (Table 7.1) and more undoubtedly remain to be characterized. Factors that inhibit cell growth also exist, e.g. interferons (IFNs) and tumour necrosis factor (TNF) inhibit proliferation of various cell types.
Some growth factors may be classified as cytokines, e.g. ILs, transforming growth factor-b (TGF-b) and colony stimulating factors (CSFs). Others, e.g. insulin-like growth factors (IGFs) are not members of this family. Each growth factor has a mitogenic (promotes cell division) effect on a characteristic range of cells. While some such factors affect only a few cell types, most stimulate the growth of a wide range of cells. The range of growth factors considered in this chapter is limited to those that have not received attention in previous chapters.
The ability of such factors to promote accelerated cellular growth and division has predictably attracted the attention of the pharmaceutical industry. The clinical potential of a range of such factors, e.g. to accelerate the wound-healing process, is currently being assessed in various clinical trials (Table 7.2).
GROWTH FACTORS AND WOUND HEALING
The wound-healing process is complex and as yet not fully understood. The area of tissue damage becomes the focus of various events, often beginning with immunological and inflammatory reactions. The various cells involved in such processes, as well as additional cells at the site of the wound, also secrete various growth factors. These mitogens stimulate the growth and activation of various cell types, including fibroblasts (which produce collagen and elastin precursors, and ground substance), epithelial cells (e.g. skin cells) and vascular endothelial cells. Such cells advance healing by promoting processes such as granulation (growth of connective tissue and small blood vessels at the healing surface) and subsequent epithelialization. The growth factors that appear most significant to this process include fibroblast growth factors (FGFs), transforming growth factors (TGFs), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF).
Wounds can be categorized as acute (healing quickly on their own) or chronic (healing slowly, and often requiring medication). Chronic wounds, such as ulcers (Table 7.3), occur if some
Biopharmaceuticals: Biochemistry and Biotechnology, Second Edition by Gary Walsh John Wiley & Sons Ltd: ISBN 0 470 84326 8 (ppc), ISBN 0 470 84327 6 (pbk)
Table 7.1. Overview of some polypeptide growth factors. Many can be grouped into families on the basis of amino acid sequence homology, or the cell types affected. Most growth factors are produced by more than one cell type and display endocrine, paracrine or autocrine effects on target cells by interacting with specific cell surface receptors
Growth factor Major target cells
Interleukins Various, mainly cells mediating immunity and inflammation
Interferon-g Mainly lymphocytes and additional cells mediating immunity (and
Colony stimulating factors Mainly haemopoietic cells
Erythropoietin Erythroid precursor cells
Thrombopoietin Mainly megakaryocytes
Neurotrophic factors Several, but mainly neuronal cell populations
Insulin-like growth factors A very wide range of cells found in various tissue types
Epidermal growth factor Various, including epithelial and endothelial cells and fibroblasts
Platelet-derived growth factor Various, including fibroblasts, glial cells and smooth muscle cells
Fibroblast growth factors Various, including fibroblasts, osteoblasts and vascular endothelial
Transforming growth factors-a Various
Leukaemia inhibitory factor Mainly various haemopoietic cells
Table 7.2. Some growth factors which may have significant future therapeutic application, and the
conditions they aim to treat
Growth factor Possible medical indication