Growth factors identified for cosmetic applications
Growth factors have been identified as the next generation ingredient for anti-aging products by opinion leaders in the cosmetic industry and an increasing number of cosmetic companies are using recombinant, bioactive proteins in their products. Below is a short description of some of the growth factors that have been targeted as potential active ingredients in cosmetics.
EGF Epidermal growth factor
Epidermal Growth Factor (EGF) is a potent growth factor that stimulates the proliferation of various epidermal and epithelial cells. Recombinant human EGF is a 6.2 kDa globular protein containing 53 amino acid residues, including 3 intramolecular disulfide-bonds.
EGF was the first growth factor to be discovered, led to the 1986 Nobel Prize in Physiology or Medicine for Stanley Cohen. It operates via the EGF receptor on epidermal cells and fibrobasts.
Clinical studies have demonstrated the efficacy of EGF in promoting wound healing, improvements in skin appearance and structure.
KGF Keratinocyte growth factor
Keratinocyte Growth Factor (KGF/FGF-7) is one of 23 known members of the FGF family. Proteins of this family play a central role during prenatal development and postnatal growth and regeneration of variety of tissues, by promoting cellular proliferation and differentiation. KGF/FG-7 is a mitogen factor specific for epithelial cells and keratinocytes and signals through FGFR 2b. KGF/FGF-7 plays a role in kidney and lung development, angiogenesis, and wound healing.
KGF has been associated with protecting the skin from chemical and physical insults, especially UV radiation and oxygen; a drug used in during radiation therapy has been developed to heal the damaging powers of the radiation, Kepivance® is indicated to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support.
TGF-beta Transforming growth factor beta1
Human Transforming Growth Factor-beta1 (TGF-beta1) is a member of a super-family of homologous, disulfide-linked, homo-dimeric proteins that regulate the proliferation and differentiation of normal and transformed cells. Human TGF-beta1 is a 25.0 kDa protein with each subunit containing 112 amino acid residues. Many of the biological activities of TGF-beta point to the fact that it may be a potent regulator of Wound healing and of bone fracture healing. TGF-beta plays an important role in the development of ossification of the posterior longitudinal ligament of the cervical spine. The factor may be helpful in the treatment of traumatic tissue injuries and in the treatment of osteoporosis. (Induce migration of fibroblasts to the site of damage. TGF-beta stimulates angiogenesis and is an important regulator of the extracellular matrix (ECM) by inhibiting ECM-degrading proteases and up-regulating the synthesis of protease inhibitors.
Induce synthesis of extracellular matrix components such as collagen, gycosaminoglycans and elastin. TGF-B controls fibroblst activation of collagen synthesis.
Various cell types secrete TGF-b, and various cell types have receptors for TGF-b, their actions may be inhibitory or stimulatory depending on the presence of other growth factors or interaction with the extracellular matrix. At low concentrations the TGF-b stimulates fibroblast proliferation while they induce differentiation at higher concentrations.
Some clinical studies including TGF-b have shown improvements of aged skin with significant improved wrinkle score. Some clinical studie have shown positive anti aging effects after applying a cream including TGF-b.
PDGF Platelet-derived growth factor BB
Platelet-derived growth factor BB (rhPDGF-BB) is a potent wound healing growth factor and stimulator of the proliferation and recruitment of both periodontal ligament (PDL) and bone cells.
Induce migration of fibroblasts to the site of damage, induce synthesis of extracellular matrix components such as collagen, gycosaminoglycans and elastin.
IGF-1 Insulin-like growth factor 1
Insulin Like Growth Factor-I (IGF-I) is a polypeptide growth factor which stimulates the proliferation of a wide range of cell types including muscle, bone, and cartilage tissue. It is produced also locally in many other tissues including kidney, heart, lung, fat tissues, and various glandular tissues. The factor may be valuable also in fracture healing and in the treatment of postmenopausal osteoporosis.
Induces synthesis of extracellular matrix components such as collagen, gycosaminoglycans and elastin.
FGF-basic Fibroblast growth factor, basic
Proteins of this family play a central role during prenatal development and postnatal growth and regeneration of a variety of tissues, by promoting cellular proliferation and differentiation.
Induce synthesis of extracellular matrix components such as collagen, gycosaminoglycans and elastin. They can guide angiogenesis
FGF-acidic Fibroblast growth factor, acidic
In vitro, FGF-a participates in various cellular functions including proliferation, differentiation and cell migration. FGF-a is a potent mitogen in vitro for many cells of ectodermal and mesodermal embryonic origin including skin-derived epidermal keratinocytes, dermal fibroblasts and vascular endothelial cells. FGF-a is one of the angiogenesis factors and has been shown to promote wound healing.
Other Growth factors which might be of interest
LIF Leukemia Inhibitory factor
LIF is a heavily and variably glycosylated 58 kDa protein. with a length of 179 amino acids. Glycosylation does not appear to be essential for bioactivity. Leukemia inhibitory factor (“LIF”), an LIF analogue, an LIF mimetic, a product capable of stimulating the expression of endogenous LIF and mixtures thereof are useful for maintaining and/or stimulating the regenerative power of a population of human undifferentiated skin stem cells and/or epidermal progenitors, and are also useful for treating dry and/or chapped and/or aged skin and/or hair loss, as well as for treating skin burns and promoting skin regeneration and/or cicatrization.
VEGF Vascular endothelial growth factor-121
Vascular Endothelial Cell Growth Factor (VEGF) is a secreted homo-dimeric protein that stimulates endothelial cell growth, angiogenesis and capillary permeability. VEGF is distinct among other growth factors in that its mitogenic activity is specific for endothelial cells and it is the only growth factor that stimulates vascular permeability.
TNF-alpha Tumor necrosis factor-alpha
TNF-alpha is a pleiotrophic pro-inflammatory cytokine secreted by various cells including adipocytes, activated monocytes, macrophages, B cells, T cells and fibroblasts. It belongs to the TNF family of ligands and signals through two receptors, TNFR1 and TNFR2. TNF-alpha is cytotoxic to a wide variety of tumor cells and is an essential factor in mediating the immune response against bacterial infections. TNF-alpha also plays a role in the induction of septic shock, auto immune diseases, rheumatoid arthritis, inflammation, and diabetes.
GCS Granulocyte colony-stimulating factor
G-CSF is a hematopoietic growth factor that stimulates the development of committed progenitor cells to neutrophils and enhances the functional activities of the mature end-cell. It is produced in response to specific stimulation by a variety of cells including macrophages, fibroblasts, endothelial cells and bone marrow stroma. G-CSF is being used clinically to facilitate hematopoietic recovery after bone marrow transplantation
SCF Stem cell factor
SCF induces differentiation in lymphoid and erythroid progenitor cells and mast cells and acts on very immature hematopoietic progenitor cells. SCF may be an important regulator of platelet production under both normal and physiologically disturbed situations.
GMCS Granulocyte macrophage colony-stimulating factor
GM-CSF is a hematopoietic growth factor that stimulates the development of neutrophils and macrophages and promotes the proliferation and development of early erythroid megakaryocytic and eosinophilic progenitor cells. It is produced in by endothelial cells, monocytes, fibroblasts and T-lymphocytes. GM-CSF inhibits neutrophil migration and enhances the functional activity of the mature end-cells.
IL-7 Interleukin-7
IL-7 stimulates the proliferation of pre-B and pro-B-cells without affecting their differentiation.
IL-7 is a hematopoietic growth factor which affects primarily early B and T cells. Produced by thymic stromal cells, spleen cells and keratinocytes, IL-7 can also co-stimulate the proliferation of mature T cells in combination with other factors such as ConA and IL-2.
IL-1b Interleukin-1b
There are two functionally almost equivalent forms of IL1, IL1-alpha and IL1-beta.
IL1-alpha and IL1-beta are biologically more or less equivalent pleiotropic factors that act locally and also systemically. IL1-beta appears to be expressed constitutively in the brain. IL1-beta induces thymocyte proliferation, by inducing IL-2 release, B-cell maturation and proliferation, mitogenic FGF-like activity. IL-1beta is a secreted cytokine.
TGF-alpha Transforming growth factor alpha
TGF-alpha is thought to be the fetal form of EGF . The physiological role of TGF-alpha is probably the control of epidermal development during development and differentiation of the cells. TGF-alpha is probably also involved in the regeneration of liver tissues.
IL-6 Interleukin-6
IL-6 is a pleiotropic cytokine that plays an important role in host defense by regulating immune and inflammatory responses. Produced by T cells, monocytes, fibroblasts, endothelial cells and keratinocytes, IL-6 has diverse biological functions. It stimulates B-cell differentiation and antibody production, synergizes with IL-3 in megakaryocyte development and platelet production, induces expression of hepatic acute-phase proteins, and regulates bone metabolism.
IL-15 Interleukin-15
IL-15 is an immunomodulating cytokine that stimulates the proliferation of T lymphocytes. IL-15 exerts its biological activites primarily on T cells. It is also essential in the development, survival and activation of NK cells.
IL-10 Interleukin-10
IL-10 is an immunosuppressive cytokine produced by a variety of mammalian cell types including macrophages, monocytes, T cells, B cells and keratinocytes. IL-10 inhibits the expression of proinflammatory cytokines such as IL-1 and TNFα. Like IL-4, IL-10 enhances humoral immune responses and attenuates cell-mediated immune reactions.
BMP4 Bone morphogenetic protein 4
Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. BMP-4 plays a role in the specification of hematopoietic tissue from the mesodermal germ layer.
IL-8 Interleukin-8
IL-8 is a proinflammatory CXC chemokine that can signal through the CXCR1 and CXCR2 receptors. It is secreted by monocytes and endothelial cells. IL-8 chemoattracts and activates neutrophils.
IL-20 Interleukin-20
IL-20 is a member of the IL-10 family of regulatory cytokines which includes IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. Members of this family share partial homology in their amino acid sequences but they are dissimilar in their biological functions. IL-20 is a hematopoietic growth factor capable of stimulating colony formation by CD34+ multipotential progenitors, but not by other progenitor cells.
T beta 4 Thymosin beta-4
Thymosin beta 4 (T beta 4) is a 4.9 kDa polypeptide that interacts with G-actin and is thought to be an important mediator in cell proliferation, migration, and differentiation. T beta 4 has been identified as a factor involved in the differentiation of human umbilical vein endothelial cells (HUVECs) cultured on Matrigel. Thymosin Beta-4 assist in regulating immune cells and is also a powerful anti-inflammatory and wound healing agent.
NGF-B Nerve growth factor-B
NGF is not a mitogen so that its name is actually a misnomer. It is mainly responsible for the survival and the differentiation and the functional activities of sensory and sympathetic neurons in the peripheral nervous system. It also plays an important role in the development and functional activities of cholinergic neurons in the central nervous system.
PIGF-1 Placental growth factor
The biologically active form of this protein is a disulfide-linked dimer. The N-glycosylated dimeric protein is secreted and, like VPF , stimulates the proliferation of endothelial cell lines and supports angiogenesis .