title: Sustained survival and maturation of adult neural stem/progenitor cells after transplantation into the injured brain.
abstract: Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells.
authors.affiliation: Department of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0631, USA. dsun@vcu.edu
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Marinella
authors.initials: M
authors.lastname: Gugliotta
authors.forename: Andrew
authors.initials: A
authors.lastname: Rolfe
authors.forename: Wendy
authors.initials: W
authors.lastname: Reid
authors.forename: A Rory
authors.initials: AR
authors.lastname: McQuiston
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
authors.forename: Harold
authors.initials: H
authors.lastname: Young
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation / Q000379:methods*