TY - JOUR
T1 - Fibroblast growth factor signaling promotes physiological bone remodeling and stem cell self-renewal
AU - Itkin, Tomer
AU - Kaufmann, Kerstin B.
AU - Gur-Cohen, Shiri
AU - Ludin, Aya
AU - Lapidot, Tsvee
N1 - Israeli Science Foundation [544/09]; European Union [HEALTH-F5-2010-261387]; The Edith Arnoff Stein Professorial Chair in Stem Cell ResearchThe authors thank the members of Lapidot's laboratory for a fruitful scientific discussion. The authors' studies presented in this review were supported in part by the Israeli Science Foundation (544/09), and the European Union (Advance Cell-based Therapies for the Treatment of Primary Immunodeficiency HEALTH-F5-2010-261387) and The Edith Arnoff Stein Professorial Chair in Stem Cell Research (T.L.).
PY - 2013/5
Y1 - 2013/5
N2 - Purpose of Review: 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. Recent Findings: 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. Summary: 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.
AB - Purpose of Review: 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. Recent Findings: 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. Summary: 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.
KW - FGF-2
KW - FGFR
KW - expansion
KW - hematopoietic stem cells
KW - microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84876296025&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/MOH.0b013e3283606162
DO - https://doi.org/10.1097/MOH.0b013e3283606162
M3 - مقالة مرجعية
C2 - 23567340
SN - 1065-6251
VL - 20
SP - 237
EP - 244
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
IS - 3
ER -
