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Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke
Institution:1. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran;2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;3. Histomorphometry & Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran;4. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;5. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;1. Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China;2. Department of Cardiovasology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China;1. State University of New York, Downstate College of Medicine, Brooklyn, NY;2. University of Rochester Medical Center, Department of Neurology, Rochester, NY;1. Department of Neurology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;2. Department of Cardiac Function, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;3. Key Unit of Methodology in Clinical Research, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;4. Tongde Hospital of Zhejiang Province, Zhejiang, China;1. Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing 400016, China;2. Department of Chronic Diseases, Yubei District Center for Disease Control and Prevention, Chongqing 401120, China;1. Department of Neurology, Stroke Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Palmer 127, 330 Brookline Ave, Boston, MA 02215, United States;2. Department of Neurology, Stroke Division, Yale New Haven Hospital, New Haven, CT, United States;1. Department of Physical Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;2. Department of Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;3. Department of Neurology, Hospital Risoleta Tolentino Neves, Belo Horizonte, MG, Brazil
Abstract:Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke.Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.
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