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Open AccessArticle

Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment

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School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
3
Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
4
Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea
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Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
6
Laboratory Animal Research Center, Samsung Biomedical Research Institute, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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Laboratory Animal Center, Osong Medical Innovation Foundation, Cheongju 28160, Korea
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Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
9
Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5524; https://doi.org/10.3390/ijms21155524
Received: 30 June 2020 / Revised: 25 July 2020 / Accepted: 30 July 2020 / Published: 1 August 2020
(This article belongs to the Special Issue Small Vessel Disease: A Whole Brain Disease)
Closely linked to Alzheimer’s disease (AD), the pathological spectrum of vascular cognitive impairment (VCI) is known to be wide and complex. Considering that multiple instead of a single targeting approach is considered a treatment option for such complicated diseases, the multifaceted aspects of mesenchymal stem cells (MSCs) make them a suitable candidate to tackle the heterogeneity of VCI. MSCs were delivered via the intracerebroventricular (ICV) route in mice that were subjected to VCI by carotid artery stenosis. VCI was induced in C57BL6/J mice wild type (C57VCI) mice by applying a combination of ameroid constrictors and microcoils, while ameroid constrictors alone were bilaterally applied to 5xFAD (transgenic AD mouse model) mice (5xVCI). Compared to the controls (minimal essential medium (MEM)-injected C57VCI mice), changes in spatial working memory were not noted in the MSC-injected C57VCI mice, and unexpectedly, the mortality rate was higher. In contrast, compared to the MEM-injected 5xVCI mice, mortality was not observed, and the spatial working memory was also improved in MSC-injected 5xVCI mice. Disease progression of the VCI-induced mice seems to be affected by the method of carotid artery stenosis and due to this heterogeneity, various factors must be considered to maximize the therapeutic benefits exerted by MSCs. Factors, such as the optimal MSC injection time point, cell concentration, sacrifice time point, and immunogenicity of the transplanted cells, must all be adequately addressed so that MSCs can be appropriately and effectively used as a treatment option for VCI. View Full-Text
Keywords: Alzheimer’s disease; vascular cognitive impairment; heterogeneity; mesenchymal stem cell; therapeutic Alzheimer’s disease; vascular cognitive impairment; heterogeneity; mesenchymal stem cell; therapeutic
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Lee, N.K.; Kim, H.; Chang, J.W.; Jang, H.; Kim, H.; Yang, J.; Kim, J.; Son, J.P.; Na, D.L. Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment. Int. J. Mol. Sci. 2020, 21, 5524.

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