Molecular Neurobiology

, Volume 54, Issue 8, pp 6198–6212 | Cite as

G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in Alzheimer’s Disease Mice via CXCR4/SDF-1 Chemotaxis

  • Cheng-Chun Wu
  • I-Fang Wang
  • Po-Min Chiang
  • Liang-Chao Wang
  • Che-Kun James ShenEmail author
  • Kuen-Jer TsaiEmail author


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.


G-CSF Bone marrow stem cells SDF-1 CXCR4 Neurogenesis Alzheimer’s disease 



The authors are grateful to Ya-Chun Hsiao for the services regarding image acquisition and analysis from the FACS-like tissue cytometry in the Center of Clinical Medicine, NCKU Hospital, and Ming-Tai Yu and Yi-Ru Gu for the technical support. This study is partly supported by NCKU Academic Summit Program and the Ministry of Science and Technology grant (MOST-105-2321-B-006-002, MOST-104-2321-B-006-010, MOST-103-2321-B-006 -028, MOST-105-2628-B-006-016-MY3, and NSC-102-2320-B-006-040-MY3).

Author Contribution

Cheng-Chun conceived and designed the study, collected and assembled the data, analyzed and interpreted the data, and wrote the manuscript. I-Fang provisioned the study material and analyzed and interpreted the data. Po-Min conceived and designed the study and collected and assembled the data. Liang-Chao conceived and designed the study and collected and assembled the data. Che-Kun James provisioned the study material and analyzed and interpreted the data. Kuen-Jer conceived and designed the study, collected and assembled the data, analyzed and interpreted the data, wrote the manuscript, and approved the final version of manuscript.

Compliance with Ethical Standards

Conflicts of Interest

The authors have no conflict of interest in this study.

Supplementary material

12035_2016_122_MOESM1_ESM.doc (1.5 mb)
ESM 1 (DOC 1524 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Cheng-Chun Wu
    • 1
    • 2
  • I-Fang Wang
    • 2
    • 3
    • 4
  • Po-Min Chiang
    • 1
    • 2
    • 5
  • Liang-Chao Wang
    • 2
    • 6
  • Che-Kun James Shen
    • 3
    • 4
    Email author
  • Kuen-Jer Tsai
    • 1
    • 2
    • 5
    Email author
  1. 1.Institute of Basic Medical ScienceNational Cheng Kung UniversityTainanTaiwan
  2. 2.Institute of Clinical MedicineNational Cheng Kung UniversityTainanTaiwan
  3. 3.Institute of Life ScienceNational Defense Medical CenterTaipeiTaiwan
  4. 4.Institute of Molecular BiologyAcademia SinicaTaipeiTaiwan
  5. 5.Center of Clinical MedicineNational Cheng Kung University HospitalTainanTaiwan
  6. 6.Division of Neurosurgery, Department of SurgeryNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan

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