Sabrina K Uppal, Toni L. Uhlendorf, Ruslan L. Nuryyev, Jacqueline Saenz, Menaga Shanmugam, Jessica Ochoa, William Van Trigt, C. Malone, Andrew P St. Julian, O. Kopyov, A. Kopyov, R. Cohen, Oxnard Ca Usa Celavie Biosciences Llc
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Celavie Biosciences have developed a multipotent, nontumorigenic human neural progenitor cell (hNPC) line shown to have the ability to migrate in situ, reducing structural and functional deficits in neurodegenerative animal models. Here, we examined whether transplanted hNPCs would reestablish the memories of Han-Wistar rats subjected to hippocampal excitotoxic lesioning. The rats were lesioned in the CA3c regions at 50 days bilaterally with the neurotoxin NMDA (1 µl containing 7.5 mg/ml; −3.5 mm AP; ±2.0 L and −2.5 V). At 54 days of age, live hNPCs (500000 cells in 5 µl cell suspension media), frozen-killed hNPCs (500000 cells/5 µl), HEK293T cells (500000 cells/5 µl) or vehicle (cell suspension media; 5 µl) were bilaterally implanted directly into the NMDA damaged area. The rats were tested two weeks later with three different memory tests: novel and place-object assays and the water-maze task. Results showed that rats receiving live hNPC implantation performed significantly better in the water maze task than control groups; yet, novel and place-object test results showed no significant differences among treatments. Histology confirmed the survival of implanted hNPCs after 28 days post-implantation as well as showing neuroprotective effects. This study showed that Celavie's hNPCs were able to survive and improve some but not all hippocampal functionality, emphasizing the promise for cell replacement therapeutics for neurodegenerative disorders.","PeriodicalId":43011,"journal":{"name":"AIMS Medical Science","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Human neural progenitor cells ameliorate NMDA-induced hippocampal degeneration and related functional deficits\",\"authors\":\"Sabrina K Uppal, Toni L. Uhlendorf, Ruslan L. Nuryyev, Jacqueline Saenz, Menaga Shanmugam, Jessica Ochoa, William Van Trigt, C. Malone, Andrew P St. Julian, O. Kopyov, A. Kopyov, R. 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引用次数: 0
摘要
海马体的CA3区参与了短期记忆向长期记忆的巩固,并有助于空间导航的保留。癫痫发作和许多神经系统疾病都会对海马体的这一区域造成损害,导致记忆巩固和空间导航的缺陷。药物治疗已被证明效果有限,但细胞替代疗法已被证明更有希望。Celavie Biosciences开发了一种多能、非致瘤性的人类神经祖细胞(hNPC)系,在神经退行性动物模型中显示出原位迁移的能力,减少了结构和功能缺陷。在这里,我们研究了移植的hNPCs是否会重建海马兴奋毒性损伤的Han-Wistar大鼠的记忆。50 d双侧神经毒素NMDA(1µl含7.5 mg/ml;−3.5 mm AP;±2.0 L和−2.5 V)。54日龄时,活的hNPCs(500000个细胞,5µL细胞悬液)、冷冻杀死的hNPCs(500000个细胞/5µL)、HEK293T细胞(500000个细胞/5µL)或载体(细胞悬液;5µl)双侧直接植入NMDA损伤区。两周后,对这些大鼠进行了三种不同的记忆测试:新事物和地点-物体测试以及水迷宫任务。结果表明,接受hNPC活体植入的大鼠在水迷宫任务中的表现明显优于对照组;然而,新颖性和地点客体测试结果在不同处理之间没有显着差异。组织学证实植入的hNPCs在植入后28天存活,并显示出神经保护作用。这项研究表明,Celavie的hNPCs能够存活并改善部分(但不是全部)海马功能,强调了神经退行性疾病的细胞替代疗法的前景。
Human neural progenitor cells ameliorate NMDA-induced hippocampal degeneration and related functional deficits
It has been established that the CA3 region of the hippocampus is involved in consolidating short-term memory to long-term memory and aids in spatial navigation retention. Seizures and many neurologic diseases induce damage to that region of the hippocampus, resulting in deficits in memory consolidation and spatial navigation. Drug treatments have been proven to have limited effectiveness, but cell replacement therapy has demonstrated to be more promising. Celavie Biosciences have developed a multipotent, nontumorigenic human neural progenitor cell (hNPC) line shown to have the ability to migrate in situ, reducing structural and functional deficits in neurodegenerative animal models. Here, we examined whether transplanted hNPCs would reestablish the memories of Han-Wistar rats subjected to hippocampal excitotoxic lesioning. The rats were lesioned in the CA3c regions at 50 days bilaterally with the neurotoxin NMDA (1 µl containing 7.5 mg/ml; −3.5 mm AP; ±2.0 L and −2.5 V). At 54 days of age, live hNPCs (500000 cells in 5 µl cell suspension media), frozen-killed hNPCs (500000 cells/5 µl), HEK293T cells (500000 cells/5 µl) or vehicle (cell suspension media; 5 µl) were bilaterally implanted directly into the NMDA damaged area. The rats were tested two weeks later with three different memory tests: novel and place-object assays and the water-maze task. Results showed that rats receiving live hNPC implantation performed significantly better in the water maze task than control groups; yet, novel and place-object test results showed no significant differences among treatments. Histology confirmed the survival of implanted hNPCs after 28 days post-implantation as well as showing neuroprotective effects. This study showed that Celavie's hNPCs were able to survive and improve some but not all hippocampal functionality, emphasizing the promise for cell replacement therapeutics for neurodegenerative disorders.