Granulocyte Colony-Stimulating Factor
Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic protein that promotes the development and function of granulocytes and mobilizes stem/progenitor cells from the bone marrow. Recent studies have shown that G-CSF also directly influen
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Granulocyte Colony-Stimulating Factor Yasuyuki Fujita and Atsuhiko Kawamoto
Abstract Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic protein that promotes the development and function of granulocytes and mobilizes stem/progenitor cells from the bone marrow. Recent studies have shown that G-CSF also directly influences the activity of some non-hematopoietic cells, such as cardiomyocytes, endothelial cells, and neurons via G-CSF receptor. This chapter provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the therapeutic strategy using G-CSF for ischemic diseases. Keywords CD34+ cells • Cerebrovascular disease (CVD) • Coronary artery disease (CAD) • Endothelial progenitor cells (EPCs) • Granulocyte colony-stimulating factor (G-CSF) • Peripheral artery disease (PAD)
Y. Fujita, M.D., Ph.D. • A. Kawamoto, M.D., Ph.D. (*) Division of Vascular Regeneration, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation (IBRI) Hospital, 2-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan Vascular Regeneration Research Group, IBRI Research Center, Kobe, Hyogo, Japan Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Hyogo, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2017 Y. Higashi, T. Murohara (eds.), Therapeutic Angiogenesis, DOI 10.1007/978-981-10-2744-4_13
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Y. Fujita and A. Kawamoto
13.1 Granulocyte Colony-Stimulating Factor (G-CSF) Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic protein that promotes the maturation, proliferation, and differentiation of the precursor cells of neutrophilic granulocytes [1–3] and mobilizes stem/progenitor cells from the bone marrow (BM) into peripheral blood (PB) [4]. Clinically, G-CSF has been used for the treatment of patients suffering from chemotherapy-associated neutropenia and the collection of stem cells used in allogeneic or autologous PB stem cell (PBSC) transplantation. G-CSF is a 19.6 kD glycoprotein encoded by a single gene located on human chromosome 17 at 17q11–12 [5]. Two variant forms of this protein including 174- amino acid protein and 177-amino acid protein can be derived from differential splicing of the pre-mRNA of G-CSF [2, 6]. The 174-amino acid G-CSF is more active at stimulating proliferation of progenitor cells than the 177-amino acid G-CSF [2]. Monocyte/macrophage lineage cells are the major source of G-CSF; however, vascular endothelial cells, mesothelial cells, and fibroblasts have been found to produce G-CSF in response to inflammatory cytokines [7–10]. Production of G-CSF can be induced in vitro by appropriate stimulation with inflammatory mediators such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interferon (IFN)-β, vascular endothelial growth factor (VEGF), interleukin (IL)17 and IL-1 in endothelial cells, macrophages, epithelial cells, and fibroblasts [11–13]. G-CSF primarily acts via activation of G-CSF
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