PMID- 21608078
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20211203
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 29
IP  - 7
DP  - 2011 Jul
TI  - Combined effects of hematopoietic progenitor cell mobilization from bone marrow 
      by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the 
      brain using stromal cell-derived factor-1alpha in an Alzheimer's disease mouse model.
PG  - 1075-89
LID - 10.1002/stem.659 [doi]
AB  - Transplantation of bone marrow-derived stem cells (BMSCs) has been suggested as a 
      potential therapeutic approach to prevent neurodegenerative diseases, but it 
      remains problematic due to issues of engraftment, potential toxicities, and other 
      factors. An alternative strategy is pharmacological-induced recruitment of 
      endogenous BMSCs into an injured site by systemic administration of growth 
      factors or chemokines. Therefore, the aim of this study was to examine the 
      effects of therapy involving granulocyte colony stimulating factor 
      (G-CSF)/AMD3100 (CXCR4 antagonist) and stromal cell-derived factor-1alpha (SDF-1alpha) on 
      endogenous BM-derived hematopoietic progenitor cell (BM-HPC) recruitment into the 
      brain of an Alzheimer's disease (AD) mouse model. To mobilize BM-HPCs, G-CSF was 
      injected intraperitoneally and boosted by AMD3100. Simultaneously, these mice 
      received an intracerebral injection with SDF-1alpha to induce migration of mobilized 
      BM-HPCs into brain. We found that the memory deficit in the AD mice was 
      significantly improved by these treatments, but amyloid beta deposition was 
      unchanged. Interestingly, microglial activation was increased with alternative 
      activation of microglia to a neuroprotective phenotype. Furthermore, by 
      generating an amyloid precursor protein/presenilin 1-green fluorescent protein 
      (GFP) chimeric mouse, we ascertained that the GFP positive microglia identified 
      in the brain were BM-derived. Additionally, increased hippocampal neurogenesis 
      and improved memory was observed in mice receiving combined G-CSF/AMD3100 and 
      SDF-1alpha, but not in controls or animals receiving each treatment alone. These 
      results suggest that SDF-1alpha is an effective adjuvant in inducing migration into 
      brain of the endogenous BM-HPCs, mobilized by G-CSF/AMD3100, and that the two can 
      act synergistically to produce a therapeutic effect. This approach warrants 
      further investigation as a potential therapeutic option for the treatment of AD 
      patients in the future.
CI  - Copyright (c) 2011 AlphaMed Press.
FAU - Shin, Ji-Woong
AU  - Shin JW
AD  - Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, 
      Korea.
FAU - Lee, Jong Kil
AU  - Lee JK
FAU - Lee, Jeong Eun
AU  - Lee JE
FAU - Min, Woo-Kie
AU  - Min WK
FAU - Schuchman, Edward H
AU  - Schuchman EH
FAU - Jin, Hee Kyung
AU  - Jin HK
FAU - Bae, Jae-Sung
AU  - Bae JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Benzylamines)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cyclams)
RN  - 0 (Heterocyclic Compounds)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - S915P5499N (plerixafor)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/pathology
MH  - Animals
MH  - Benzylamines
MH  - Bone Marrow Cells/cytology/drug effects
MH  - Brain/*cytology/drug effects
MH  - Chemokine CXCL12/*administration & dosage
MH  - Chemotaxis/*drug effects
MH  - Cyclams
MH  - Disease Models, Animal
MH  - Granulocyte Colony-Stimulating Factor/*administration & dosage
MH  - Hematopoietic Stem Cell Mobilization/*methods
MH  - Hematopoietic Stem Cells/cytology/*drug effects
MH  - Heterocyclic Compounds/*administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
EDAT- 2011/05/25 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/05/25 06:00
PHST- 2011/05/25 06:00 [entrez]
PHST- 2011/05/25 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - 10.1002/stem.659 [doi]
PST - ppublish
SO  - Stem Cells. 2011 Jul;29(7):1075-89. doi: 10.1002/stem.659.