title: Fibroblast growth factor signaling promotes physiological bone remodeling and stem cell self-renewal.
abstract: OBJECTIVE
  Fibroblast growth factor (FGF) signaling activates many bone marrow cell types, including various stem cells, osteoblasts, and osteoclasts. However, the role of FGF signaling in regulation of normal and leukemic stem cells is poorly understood. This review highlights the physiological roles of FGF signaling in regulating bone marrow mesenchymal and hematopoietic stem and progenitor cells (MSPCs and HSPCs) and their dynamic microenvironment. In addition, this review summarizes the recent studies which provide an overview of FGF-activated mechanisms regulating physiological stem cell maintenance, self-renewal, and motility.
  
  
  RESULTS
  Current results indicate that partial deficiencies in FGF signaling lead to mild defects in hematopoiesis and bone remodeling. However, FGF signaling was shown to be crucial for stem cell self-renewal and for proper hematopoietic poststress recovery. FGF signaling activation was shown to be important also for rapid AMD3100 or post 5-fluorouracil-induced HSPC mobilization. In vivo, FGF-2 administration successfully expanded both MSPCs and HSPCs. FGF-induced expansion was characterized by enhanced HSPC cycling without further exhaustion of the stem cell pool. In addition, FGF signaling expands and remodels the supportive MSPC niche cells. Finally, FGF signaling is constitutively activated in many leukemias, suggesting that malignant HSPCs exploit this pathway for their constant expansion and for remodeling a malignant-supportive microenvironment.
  
  
  CONCLUSIONS
  The summarized studies, concerning regulation of stem cells and their microenvironment, suggest that FGF signaling manipulation can serve to improve current clinical stem cell mobilization and transplantation protocols. In addition, it may help to develop therapies specifically targeting leukemic stem cells and their supportive microenvironment.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Itkin
authors.forename: Kerstin B
authors.initials: KB
authors.lastname: Kaufmann
authors.forename: Shiri
authors.initials: S
authors.lastname: Gur-Cohen
authors.forename: Aya
authors.initials: A
authors.lastname: Ludin
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D016723:Bone Remodeling / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D005346:Fibroblast Growth Factors