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Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

  • Jung Hoon Choi
  • Jin Young Chung
  • Dae Young Yoo
  • In Koo Hwang
  • Ki-Yeon Yoo
  • Choong Hyun Lee
  • Bing Chun Yan
  • Jin Ok Ahn
  • Hwa Young Youn
  • Moo-Ho Won
Original Research

Abstract

Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.

Keywords

Neurogenesis Ki67 Doublecortin Subgranular zone Hippocampus 

Notes

Acknowledgments

The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee, and Ms. Hyun Sook Kim for their technical help and Seung-Hae Kwon of the Korean Basic Science Institute Chuncheon Center for technical assistance with the confocal image analyses (LSM 510 META NLO) in this study. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-001058), and by a grant (2010K000823) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, the Republic of Korea.

Supplementary material

10571_2011_9729_MOESM1_ESM.tif (3 mb)
Supplementary Fig. 1. Fluorescence image of in vitro labeled of Ad-MSCs with CM-DiI. Scale Bar = 25 μm (A-C) (TIFF 3077 kb)
10571_2011_9729_MOESM2_ESM.tif (12.3 mb)
Supplementary Fig. 2. Immunofluorescence detection of CM-DiI-labeled Ad-MSCs in the hippocampus (A-C), diencephalon (D-E), midbrain (G-H) and spinal cord (J-L). Note that Ad-MSC (arrows) are observed in the meninges of the brain except for hippocampus. 3 V, third ventricle; CA, cerebral aqueduct; CC, central canal of the spinal cord. Scale Bar = 500 μm (A-I) 350 μm (J-L) (TIFF 12638 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jung Hoon Choi
    • 1
  • Jin Young Chung
    • 2
    • 3
  • Dae Young Yoo
    • 4
  • In Koo Hwang
    • 4
  • Ki-Yeon Yoo
    • 5
  • Choong Hyun Lee
    • 6
  • Bing Chun Yan
    • 6
  • Jin Ok Ahn
    • 2
  • Hwa Young Youn
    • 2
  • Moo-Ho Won
    • 6
  1. 1.Department of AnatomyCollege of Veterinary Medicine, Kangwon National UniversityChuncheonSouth Korea
  2. 2.Department of Veterinary Internal MedicineCollege of Veterinary Medicine, Seoul National UniversitySeoulSouth Korea
  3. 3.Department of NeurologyClinical Research Institute, Seoul National University HospitalSeoulSouth Korea
  4. 4.Department of Anatomy and Cell BiologyCollege of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National UniversitySeoulSouth Korea
  5. 5.Department of Oral AnatomyCollege of Dentistry, Gangneung-Wonju National UniversityGangneungSouth Korea
  6. 6.Department of NeurobiologySchool of Medicine, Kangwon National UniversityChuncheonSouth Korea

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