development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells开发大脑中动脉闭塞模型在非人类灵长类动物和输液安全研究注入人类间充质干细胞.pdfVIP

Development of a Middle Cerebral Artery Occlusion Model in the Nonhuman Primate and a Safety Study of I.V. Infusion of Human Mesenchymal Stem Cells Masanori Sasaki1,2,3, Osamu Honmou1,2,4, Christine Radtke1,2,5, Jeffery D. Kocsis1,2* 1 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Center for Neuroscience and Regeneration Research, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, United States of America, 3 Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Japan, 4 Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan, 5 Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany Abstract Background: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP) models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA) in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs) derived from human bone marrow. Methods: The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI) were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release) in the 3-hour occlusion model. Results: During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern