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Effect of Placenta-Derived Mesenchymal Stem Cells in a Dementia Rat Model via Microglial Mediation: a Comparison between Stem Cell Transplant Methods

 Jae Sung Cho  ;  Jihyeon Lee  ;  Da Un Jeong  ;  Han Wool Kim  ;  Won Seok Chang  ;  Jisook Moon  ;  Jin Woo Chang 
 YONSEI MEDICAL JOURNAL, Vol.59(3) : 406-415, 2018 
Journal Title
Issue Date
Animals ; Monoclonal Antibodies ; Cell Differentiation ; Dementia/*therapy ; Animal Disease Models ; Female ; Hippocampus ; Humans ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology/*metabolism/pathology ; Microglia ; Neuroglia/*metabolism ; Placenta/cytology/*metabolism/pathology ; Pregnancy ; Rats ; Sprague-Dawley Rats ; Type 1 Ribosome Inactivating Proteins
Placenta ; cholinergic neurons ; dementia ; hipppocampus ; mesenchymal stem cells ; microglia
PURPOSE: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
Cho, Jae Sung(조재성)
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