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Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of glycoproteins that regulate hematopoietic cell proliferation, differentiation, and function. It is a key cytokine involved in the production of neutrophils and the stimulation of granulocyte colony formation from hematopoietic progenitor cells (Metcalf and Nicola). G-CSF causes a range of effects including a transient reduction of SDF-1 expression (Petit et al.), the activation of metalloproteases that cleave VCAM-1 (Levesque et al.), and the release of norepinephrine from the sympathetic nervous system (Katayama et al.), leading to the release or mobilization of hematopoietic stem cells from the bone marrow into the periphery. The G-CSF receptor is expressed on a variety of hematopoietic cells, including myeloid-committed progenitor cells, neutrophils, granulocytes, and monocytes. In addition to hematopoietic cells, G-CSF is also expressed in cardiomyocytes, neuronal cells, mesothelial cells, and endothelial cells. Mouse G-CSF was first purified from cultures of the WEHI-3B myelomonocytic leukemia cell line as the inducer of the terminal differentiation of WEHI-3B and other myeloid leukemia cell lines (Nicola et al.). It was later cloned in monkey COS cells from a cDNA library prepared with mRNA derived from mouse fibrosarcoma NFSA cells that produce G-CSF constitutively (Tsuchiya et al.). Binding of G-CSF to its receptor leads to activation of the JAK/STAT, MAPK, PI3K, and AKT signal transduction pathways.

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Interleukin-8 (IL-8) is a member of the CXC subfamily of chemokines and is produced by leukocytic cells (monocytes, T cells, neutrophils, and natural killer cells) and non-leukocytic somatic cells (endothelial cells, fibroblasts, and epithelial cells), with the most prominent source being monocytes and macrophages. Its production is induced by inflammatory stimuli, such as IL-1. IL-8, also known as CXCL8, activates neutrophils inducing chemotaxis, exocytosis, and the respiratory burst (Baggiolini and Clark-Lewis; Mukaida). IL-8 is considered one of the most potent neutrophil chemoattractants in inflammation and binds to two different chemokine receptors on leukocytes: the G protein-coupled receptors CXCR1 and CXCR2 (Hoffmann et al.; de Oliveira et al.). IL-8 has angiogenic effects on human intestinal microvascular endothelial cells in vitro that are mediated by CXCR2 (Heidemann et al.). IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastasis and has been reported to be involved in regulating breast cancer stem-like cells (Singh et al.). IL-8 also has proangiogenic properties in inflammatory diseases of the conjunctiva, cornea, iris, retina, and orbit (Ghasemi et al.). It was also shown that a major T cell effector function in human newborns is IL-8 production, which has the potential to activate antimicrobial neutrophils and gamma/delta T cells (Gibbons et al.). A variety of human pathogens, such as HIV and Mycobacterium tuberculosis, have been shown to induce IL-8 production by monocytes and macrophages (Friedland et al.; Meddows-Taylor et al.).

Supplier: STEMCELL Technologies

Interleukin 17A (IL-17A) is the founding member of the family of cytokines that includes Interleukin 17B through Interleukin 17F. It is a potent proinflammatory cytokine that plays a key role in defense against pathogens. IL-17A and IL-17F signal as homodimers or heterodimers through the same receptor, and activate NF-kB, MAPK, and C/EBP pathways (Gaffen). IL-17A receptor is expressed on a variety of cell types, including hematopoietic cell compartments. IL-17A is produced by T helper 17 cells, CD8+ T cells, γδ T cells, natural killer T cells, B cells, neutrophils, innate lymphoid cells and mesenchymal stromal cells (MSCs; Zenobia and amp; Hajishengallis; Mojsilovic et al.). IL-17A receptor is expressed at particularly high levels on stromal cells, including MSCs. IL-17A increases the frequency and the average size of colony-forming units-fibroblast derived from bone marrow, as well as the proliferation of bone marrow-derived MSCs. IL-17A suppresses osteogenic differentiation and bone formation of bone marrow-derived MSCs. The action of IL-17A on hematopoiesis is deeply reliant on the microenvironment and the induction of other regulators. In healthy mouse bone marrow, IL-17A stimulates myeloid and early stage erythroid progenitor cells but inhibits late stage erythroid progenitor cells (Mojsilovic et al.).

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Macrophage colony-stimulating factor (M-CSF) is a homodimeric glycoprotein growth factor that regulates proliferation and differentiation of myeloid hematopoietic progenitors to mononuclear phagocytic cell lineages, including monocytes, macrophages, and osteoclasts. M-CSF is a crucial factor for the development of tissue-resident macrophages in most tissues (Ginhoux andamp; Jung). It is required for the maturation and activation of monocytes and macrophages, and regulates inflammatory responses in conjunction with other stimuli such as IFN-γ, LPS, and IL-4 (Murray et al.). M-CSF is also required for bone resorption by osteoclasts, and is involved in the development and regulation of placenta, mammary gland, and brain. M-CSF is produced by monocytes, fibroblasts, osteoclasts, stromal cells, endothelial cells, and tumor cells (Chockalingam andamp; Ghosh). M-CSF exerts its biological effects by signaling through a receptor tyrosine kinase (CSF-1R or M-CSF-R) encoded by the c-fms proto-oncogene (Hamilton). CSF-1R shares similar structural features with other growth factor receptors, including the stem cell factor (SCF) receptor, platelet-derived growth factor receptor (PDGF-R), and Flt3/Flk-2 receptor tyrosine kinase. Stimulation of the CSF-1R upon binding to M-CSF activates MAPK, PI3K, and PLCγ signaling pathways (Chockalingam andamp; Ghosh). Human and mouse M-CSF sequences are highly conserved both at nucleotide and amino acid levels (80% homology; DeLamarter et al.). This product is animal component-free.

Supplier: STEMCELL Technologies

Platelet-derived growth factor (PDGF) is a dimeric glycoprotein consisting of two disulfide bridge-stabilized polypeptide chains, A and B, which are assembled as heterodimers (PDGF-AB) or homodimers (PDGF-AA and PDGF-BB) (Fretto et al.; Westermark and Heldin). PDGF signals through the receptor tyrosine kinases PDGFRalpha and PDGFRbeta. It has been shown that PDGF-induced migration involves signaling pathways involving MEK/ERK, EGFR, Src, and PI3K/AKT (Kim et al.). PDGF is a potent mitogen for cells of mesenchymal origin, such as fibroblasts, glial cells, and vascular smooth muscle cells. PDGF has been implicated in pathogenesis of atherosclerosis, glomerulonephritis, cancer, and in the contraction of vascular smooth muscle cells of rat aortic tissues (Fretto et al.; Sachinidis et al.). It has been suggested that PDGF-AA is an important autocrine regulator of vascular endothelial growth factor (VEGF) expression in non-small cell lung carcinomas (Shikada et al.). PDGF-AA also mediates proliferation of oligodendrocyte progenitor cells and oligodendrocyte lineage differentiation through the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Hu et al.). PDGF-AA is commonly used to differentiate human pluripotent stem cell (hPSC)-derived neural progenitor cells into oligodendrocyte precursor cells (Piao et al.).

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Stem cell factor (SCF) is an early-acting cytokine that plays a pivotal role in the regulation of embryonic and adult hematopoiesis. SCF promotes cell survival, proliferation, differentiation, adhesion, and functional activation of cells at multiple levels of the hematopoietic hierarchy. Together with other cytokines such as thrombopoietin and Flt3/Flk-2 Ligand, SCF is commonly used to promote expansion of primitive hematopoietic stem cells and multi-potent progenitor cells in culture (Huang et al.; Kent et al.). In synergy with various growth factors, including IL-2, IL-3, IL-6, IL-7, G-CSF, and erythropoietin, SCF increases proliferation and differentiation of myeloid and erythroid progenitor cells and a subset of lymphoid progenitor cells (Broudy). In the mouse, SCF is essential during fetal gonadal development (Mauduit). It is produced by stromal cells in the fetal liver, bone marrow, and thymus, in the central nervous system, in keratinocytes, and in the gut mucosa, and can function as a chemotactic and chemokinetic factor. SCF exists in two biologically active splice forms: a soluble and a transmembrane isoform. Upon binding to its receptor (c-kit tyrosine kinase receptor; CD117), it activates PI3K, JAK/STAT, and MAPK pathways. SCF and signaling from c-kit has also been reported to play an important role in pigmentation, fertility, vasculogenesis, motility of the gut via c-kit-positive interstitial cells of Cajal, and in the migration of neuronal stem and progenitor cells to sites of injury in the brain (Lennartsson and Ronnstrand).

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Flt3/Flk-2 (Fms-like tyrosine kinase 3/fetal liver kinase-2) Ligand is a hematopoietic cytokine that plays an important role as a co-stimulatory factor in the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells and in the development of the immune system (Hannum et al.). Flt3/Flk-2 Ligand, together with stem cell factor and thrombopoietin, is commonly used to promote expansion of primitive CD34+ hematopoietic cells in culture. In combination with myeloid cytokines such as GM-CSF, G-CSF, or M-CSF, Flt3/Flk-2 Ligand enhances the growth and numbers of clonogenic myeloid progenitor cells. In synergy with the interleukins IL-3, IL-4, IL-7, IL-11, IL-12, IL-15, and GM-CSF and TNF-α, Flt3/Flk-2 Ligand regulates the development of various lymphoid progenitor cells, including dendritic cell, B cell, T cell, and NK cell progenitors. In contrast, Flt3/Flk-2 Ligand has no significant effect on erythropoiesis or megakaryopoiesis (Drexler andamp; Quentmeier; Wodnar-Filipowicz). Flt3/Flk-2 Ligand exists as membrane-bound and soluble isoforms. Both isoforms are biologically active and signal through the class III tyrosine kinase receptor (Flt3/Flk-2, CD135; Rosnet et al.). Flt3/Flk-2 Ligand is produced by a variety of cell types, including uncommitted and committed hematopoietic cells and stromal fibroblasts, whereas expression of the Flt3/Flk-2 receptor is restricted to CD34+ hematopoietic stem and progenitor cells. Flt3/Flk-2 receptor is also expressed on leukemic cells and outside the hematopoietic system in the brain, placenta, and testis (Drexler andamp; Quentmeier; Hannum et al.).

Supplier: STEMCELL Technologies

Flt3/Flk-2 (Fms-like tyrosine kinase 3/fetal liver kinase-2) ligand is a hematopoietic cytokine that plays an important role as a co-stimulatory factor in the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells and the development of the immune system (Lyman et al.; Rosnet et al.). Flt3/Flk-2 ligand, together with stem cell factor and thrombopoietin, is commonly used to promote expansion of primitive hematopoietic cells in culture. In combination with myeloid cytokines such as GM-CSF, G-CSF, or M-CSF, Flt3/Flk-2 ligand enhances the growth and numbers of clonogenic myeloid progenitor cells. In synergy with IL-3, IL-4, IL-7, IL-11, IL-12, IL-15, GM-CSF, and TNF-α, Flt3/Flk-2 ligand regulates the development of various lymphoid progenitor cells, including dendritic cell, B cell, T cell, and NK cell progenitors. In contrast, Flt3/Flk-2 ligand has no significant effect on erythropoiesis or megakaryopoiesis (Drexler and Quentmeier; Wodnar-Filipowicz). Flt3/Flk-2 ligand exists as membrane-bound and soluble isoforms. Both isoforms are biologically active and signal through the class III tyrosine kinase receptor (Flt3/Flk-2, CD135; Rosnet et al.). Flt3/Flk-2 ligand is produced by a variety of cell types, including uncommitted and committed hematopoietic cells and stromal fibroblasts, whereas expression of the Flt3/Flk-2 receptor is restricted to CD34+ hematopoietic stem and progenitor cells. Flt3/Flk-2 receptor is also expressed outside the hematopoietic system in the brain, placenta, and testis (Drexler and Quentmeier; Hannum et al.).

Supplier: STEMCELL Technologies

Flt3/Flk-2 (Fms-like tyrosine kinase 3/fetal liver kinase-2) Ligand is a hematopoietic cytokine that plays an important role as a co-stimulatory factor in the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells and the development of the immune system (Hannum et al.). Flt3/Flk-2 Ligand, together with stem cell factor and thrombopoietin, is commonly used to promote expansion of primitive CD34+ hematopoietic cells in culture. In combination with myeloid cytokines such as GM-CSF, G-CSF, or M-CSF, Flt3/Flk-2 Ligand enhances the growth and numbers of clonogenic myeloid progenitor cells. In synergy with the interleukins IL-3, IL-4, IL-7, IL-11, IL-12, IL-15, and GM-CSF and TNF-α, Flt3/Flk-2 Ligand regulates the development of various lymphoid progenitor cells, including dendritic cell, B cell, T cell, and NK cell progenitors. In contrast, Flt3/Flk-2 Ligand has no significant effect on erythropoiesis or megakaryopoiesis (Drexler and Quentmeier; Wodnar-Filipowicz). Flt3/Flk-2 Ligand exists as membrane-bound and soluble isoforms. Both isoforms are biologically active and signal through the class III tyrosine kinase receptor (Flt3/Flk-2, CD135; Rosnet et al.). Flt3/Flk-2 Ligand is produced by a variety of cell types, including uncommitted and committed hematopoietic cells and stromal fibroblasts, whereas expression of the Flt3/Flk-2 receptor is restricted to CD34+ hematopoietic stem and progenitor cells. Flt3/Flk-2 receptor is also expressed on leukemic cells and outside the hematopoietic system in the brain, placenta, and testis (Drexler and Quentmeier; Hannum et al.). This product is animal component-free.