Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Protect Against Neuronal Cell Death and Ameliorate Motor Deficits in Niemann Pick Type C1 Mice
Authors: Seo, Yoojin; Seo, Yoojin; Yang, Se-Ran; Yang, Se-Ran; Jee, Min Ki; Jee, Min Ki; Joo, Eun Kyung; Joo, Eun Kyung; Roh, Kyung-Hwan; Roh, Kyung-Hwan; Seo, Min-Soo; Seo, Min-Soo; Han, Tae Hee; Han, Tae Hee; Lee, So Yeong; Lee, So Yeong; Ryu, Pan Dong; Ryu, Pan Dong; Jung, Ji-Won; Jung, Ji-Won; Seo, Kwang-Won; Seo, Kwang-Won; Kang, Soo-Kyung; Kang, Soo-Kyung; Kang, Kyung-Sun; Kang, Kyung-Sun
Source: Cell Transplantation, Volume 20, Number 7, July 2011 , pp. 1033-1047(15)
Publisher: Cognizant Communication Corporation
Abstract:Niemann Pick disease type C1 (NPC) is an autosomal recessive disease characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities to ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage. This transplantation resulted in the recovery of motor function in the Rota Rod test and impaired cholesterol homeostasis leading to increased levels of cholesterol efflux-related genes such as LXRα, ABCA1, and ABCG5 while decreased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase were observed in NPC mice. In the cerebrum, hUCB-MSCs enhanced neuronal cell survival and proliferation, where they directly differentiated into electrically active MAP2-positive neurons as demonstrated by whole-cell patch clamping. In addition, we observed that hUCB-MSCs reduced Purkinje neuronal loss by suppression of inflammatory and apoptotic signaling in the cerebellum as shown by immunohistochemistry. We further investigated how hUCB-MSCs enhance cellular survival and inhibit apoptosis in NPC mice. Neuronal cell survival was associated with increased PI3K/AKT and JAK2/STAT3 signaling; moreover, hUCB-MSCs modulated the levels of GABA/glutamate transporters such as GAT1, EAAT2, EAAT3, and GAD6 in NPC mice as assessed by Western blot analysis. Taken together, our findings suggest that hUCB-MSCs might play multifunctional roles in neuronal cell survival and ameliorating motor deficits of NPC mice.
Document Type: Research Article
Affiliations: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
Publication date: July 1, 2011
- Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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- By this author: Seo, Yoojin ; Seo, Yoojin ; Yang, Se-Ran ; Yang, Se-Ran ; Jee, Min Ki ; Jee, Min Ki ; Joo, Eun Kyung ; Joo, Eun Kyung ; Roh, Kyung-Hwan ; Roh, Kyung-Hwan ; Seo, Min-Soo ; Seo, Min-Soo ; Han, Tae Hee ; Han, Tae Hee ; Lee, So Yeong ; Lee, So Yeong ; Ryu, Pan Dong ; Ryu, Pan Dong ; Jung, Ji-Won ; Jung, Ji-Won ; Seo, Kwang-Won ; Seo, Kwang-Won ; Kang, Soo-Kyung ; Kang, Soo-Kyung ; Kang, Kyung-Sun ; Kang, Kyung-Sun