Neuroprotective Effect of Human Mesenchymal Stem Cells in an Animal Model of Double Toxin-Induced Multiple System Atrophy Parkinsonism
Authors: Park, Hyun-Jung; Bang, Giyoon; Lee, Bo Ra; Kim, Hyun Ok; Lee, Phil Hyu
Source: Cell Transplantation, Volume 20, Number 6, June 2011 , pp. 827-835(9)
Publisher: Cognizant Communication Corporation
Abstract:Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder of unknown etiology featuring parkinsonism, ataxia, and autonomic failure in any combination. Because disease progression in MSA is rapid and no drug treatment consistently benefits MSA patients in the long term, neuroprotective or regenerative strategies may be invaluable in the management of MSA patients. In this study, we investigated whether human mesenchymal stem cells (hMSCs) had a protective effect on MSA using an animal model of double-toxin-induced MSA parkinsonism (MSA-P). MSA-P was established with coinjections of MPTP and 3-NP; hMSCs were injected into the tail vein 1 day after the last toxin injection. Three groups of mice were compared (i.e., control, MPTP + 3-NP, and MPTP + 3-NP with hMSC treatment) through histopathological, behavioral, and Western blot analyses. In the substantia nigra (SN) and the striatum, 2.0% and 3.8% of total injected hMSCs were observed, respectively. Compared with double-toxin-treated mice, hMSC treatment in double-toxin-treated mice significantly increased survival of TH- and NeuN-immunoreactive cells in the SN and the striatum, with coincident improvement in motor behavior. Additionally, hMSC treatment significantly decreased double-toxin-induced microglial and astroglial activation in the SN and striatum. Western blot analysis showed that hMSC administration in double-toxin-treated mice increased the expression of p-Akt and Bcl-2 and decreased Bax and cytochrome c expression. This study demonstrates that hMSC treatment protected against loss of neurons in the SN and the striatum induced by double toxin exposure, which may be mediated by modulation of inflammatory and cell survival and death signaling-pathway as the hMSCs migrated from the peripheral circulation into the SN and striatum.
Document Type: Research Article
Affiliations: Neuroscience Graduate Program, Ajou University School of Medicine, Suwon, South Korea
Publication date: June 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.