title: G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in Alzheimer's Disease Mice via CXCR4/SDF-1 Chemotaxis.
abstract: Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Cheng-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.|Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chiang
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.|Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Liang-Chao
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Institute of Life Science, National Defense Medical Center, Taipei, Taiwan. ckshen@imb.sinica.edu.tw.|Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. ckshen@imb.sinica.edu.tw.
authors.forename: Che-Kun James
authors.initials: CJ
authors.lastname: Shen
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan. kjtsai@mai.ncku.edu.tw.|Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan. kjtsai@mai.ncku.edu.tw.|Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. kjtsai@mai.ncku.edu.tw.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
mesh_terms: D000544:Alzheimer Disease; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor
keywords: Alzheimer’s disease; Bone marrow stem cells; CXCR4; G-CSF; Neurogenesis; SDF-1