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Mesenchymal Stem Cells Stimulate Endogenous Neurogenesis in the Subventricular Zone of Adult Mice

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Abstract

Mammalian neurogenesis has been demonstrated in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. However, the low rate and the restricted long term survival of newborn cells limit the restorative ability of this process. Adult bone marrow derived mesenchymal stem cells (MSCs) have been extensively studied due to their wide therapeutic potential. The aim of this study was to determine if MSC transplantation to the normally restrictive SVZ of mice housed in an enriched environment stimulates endogenous neurogenesis. In the presented study 30 C57BL/6 female mice were divided into 3 groups: standard environment injected with phosphate buffered saline (PBS) and enriched environment injected with either PBS or MSCs. Bromodeoxyuridine was injected for 6 days, and 3 weeks later the mice were sacrificed and the brain tissue analyzed immunohistochemically. PBS-treated mice housed in enriched cages showed augmented neurogenesis in the SGZ but not the SVZ. MSC transplantation was associated with increased proliferation and neuronal differentiation of neural progenitors within the SVZ and an increase in the proportion of the newborn neurons out of the total proliferating cells. Histological analysis confirmed the survival of a significant amount of the transplanted cells at least 3 weeks after transplantation, and the presence of brain-derived neurotrophic factor expression. To our knowledge, this is the first study to show that MSCs might interfere with the tight regulation of the SVZ, independent of the induced brain lesion.

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Abbreviations

BMP:

bone morphogenic protein

BDNF:

brain-derived neurotrophic factor

BrdU:

bromodeoxyuridine

GFAP:

glial fibrillary acidic protein

MSCs:

mesenchymal stem cells

NeuN:

neuronal nuclei

PBS:

phosphate buffered saline

SGZ:

subgranular zone

SVZ:

subventricular zone

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Acknowledgments

This work was performed in partial fulfillment of the requirements for a Ph.D. degree of I.K. The authors thank Dorit Trudler for her help with the cell quantifications. The authors gratefully acknowledge the Norma and Alan Aufzein Chair for Parkinson’s Disease Research and the Devora Eleonora Kirshman Fund for Research of Parkinson’s Disease, Tel Aviv University.

Conflict of Interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Neurosciences, Felsenstein Medical Research Center, Beilinson Campus and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Inna Kan, Yael Barhum, Eldad Melamed & Daniel Offen

  2. Felsenstein Medical Research Center, Beilinson Campus, Petach Tikva, 49100, Israel

    Inna Kan

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  1. Inna Kan
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Correspondence to Inna Kan.

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Kan, I., Barhum, Y., Melamed, E. et al. Mesenchymal Stem Cells Stimulate Endogenous Neurogenesis in the Subventricular Zone of Adult Mice. Stem Cell Rev and Rep 7, 404–412 (2011). https://doi.org/10.1007/s12015-010-9190-x

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