title: Behavioral and histopathological assessment of adult ischemic rat brains after intracerebral transplantation of NSI-566RSC cell lines.
abstract: Stroke is a major cause of death and disability, with very limited treatment option. Cell-based therapies have emerged as potential treatments for stroke. Indeed, studies have shown that transplantation of neural stem cells (NSCs) exerts functional benefits in stroke models. However, graft survival and integration with the host remain pressing concerns with cell-based treatments. The current study set out to investigate those very issues using a human NSC line, NSI-566RSC, in a rat model of ischemic stroke induced by transient occlusion of the middle cerebral artery. Seven days after stroke surgery, those animals that showed significant motor and neurological impairments were randomly assigned to receive NSI-566RSC intracerebral transplants at two sites within the striatum at three different doses: group A (0 cells/µl), group B (5,000 cells/µl), group C (10,000 cells/µl), and group D (20,000 cells/µl). Weekly behavioral tests, starting at seven days and continued up to 8 weeks after transplantation, revealed dose-dependent recovery from both motor and neurological deficits in transplanted stroke animals. Eight weeks after cell transplantation, immunohistochemical investigations via hematoxylin and eosin staining revealed infarct size was similar across all groups. To identify the cell graft, and estimate volume, immunohistochemistry was performed using two human-specific antibodies: one to detect all human nuclei (HuNu), and another to detect human neuron-specific enolase (hNSE). Surviving cell grafts were confirmed in 10/10 animals of group B, 9/10 group C, and 9/10 in group D. hNSE and HuNu staining revealed similar graft volume estimates in transplanted stroke animals. hNSE-immunoreactive fibers were also present within the corpus callosum, coursing in parallel with host tracts, suggesting a propensity to follow established neuroanatomical features. Despite absence of reduction in infarct volume, NSI-566RSC transplantation produced behavioral improvements possibly via robust engraftment and neuronal differentiation, supporting the use of this NSC line for stroke therapy.
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Quach
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wu
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: Tina
authors.initials: T
authors.lastname: Lam
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: Ken L
authors.initials: KL
authors.lastname: Hayama
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hazel
authors.affiliation: Neuralstem, Inc., Rockville, Maryland, United States of America.
authors.forename: Karl
authors.initials: K
authors.lastname: Johe
authors.affiliation: Neurodigitech, LLC., San Diego, California, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D002470:Cell Survival; D002544:Cerebral Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D009043:Motor Activity; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D020521:Stroke / Q000150:complications / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*