Yonsei Med J.  2018 May;59(3):406-415. 10.3349/ymj.2018.59.3.406.

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

Affiliations
  • 1Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea. jchang@yuhs.ac
  • 2Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 3General Research Institute, Gangnam CHA General Hospital, Seoul, Korea.
  • 4Department of Bioengineering, College of Life Science, CHA University, Seoul, Korea.

Abstract

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.

Keyword

Placenta; mesenchymal stem cells; dementia; hipppocampus; cholinergic neurons; microglia

MeSH Terms

Acetylcholinesterase
Animals
Choline O-Acetyltransferase
Cholinergic Neurons
Dementia*
Hippocampus
Humans
Injections, Intraventricular
Male
Mesenchymal Stromal Cells*
Methods*
Microglia
Models, Animal*
Negotiating*
Placenta
Rats*
Rats, Sprague-Dawley
Stem Cells*
Therapeutic Uses
Water
Acetylcholinesterase
Choline O-Acetyltransferase
Therapeutic Uses
Water
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