title: Intracranial Transplantation of Hypoxia-Preconditioned iPSC-Derived Neural Progenitor Cells Alleviates Neuropsychiatric Defects After Traumatic Brain Injury in Juvenile Rats.
abstract: Traumatic brain injury (TBI) is a common cause of mortality and long-term morbidity in children and adolescents. Posttraumatic stress disorder (PTSD) frequently develops in these patients, leading to a variety of neuropsychiatric syndromes. Currently, few therapeutic strategies are available to treat juveniles with PTSD and other developmental neuropsychiatric disorders. In the present investigation, postnatal day 14 (P14) Wistar rats were subjected to TBI induced by a controlled cortical impact (CCI) (velocity = 3 m/s, depth = 2.0 mm, contact time = 150 ms). This TBI injury resulted in not only cortical damages, but also posttrauma social behavior deficits. Three days after TBI, rats were treated with intracranial transplantation of either mouse iPSC-derived neural progenitor cells under normal culture conditions (N-iPSC-NPCs) or mouse iPSC-derived neural progenitor cells pretreated with hypoxic preconditioning (HP-iPSC-NPCs). Compared to TBI animals that received N-iPSC-NPCs or vehicle treatment, HP-iPSC-NPC-transplanted animals showed a unique benefit of improved performance in social interaction, social novelty, and social transmission of food preference tests. Western blotting showed that HP-iPSC-NPCs expressed significantly higher levels of the social behavior-related genes oxytocin and the oxytocin receptor. Overall, HP-iPSC-NPC transplantation exhibits a great potential as a regenerative therapy to improve neuropsychiatric outcomes after juvenile TBI.
authors.affiliation: Laboratories of Stem Cell Biology and Regenerative Medicine, Department of Neurology, Experimental Research Center and Neurological Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Zheng Zachory
authors.initials: ZZ
authors.lastname: Wei
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan Bing
authors.initials: YB
authors.lastname: Zhu
authors.forename: Todd C
authors.initials: TC
authors.lastname: Deveau
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Gu
authors.forename: Megan M
authors.initials: MM
authors.lastname: Winter
authors.forename: Jimei
authors.initials: J
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D000860:Hypoxia; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation*; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior; D013313:Stress Disorders, Post-Traumatic / Q000628:therapy*
chemical_list: D018045:Receptors, Oxytocin; C588222:oxytocin receptor, rat; D010121:Oxytocin