title: In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.
abstract: Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA) scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc) were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Do Won
authors.initials: DW
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yeona
authors.initials: Y
authors.lastname: Jin
authors.affiliation: University of Miami School of Medicine, Miami Project to Cure Paralysis, Department of Neurological Surgery, Miami, Florida, United States of America.
authors.forename: Do Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Han Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yunwoong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Youn
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Hong J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.affiliation: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy; D002470:Cell Survival; D017690:Cell Transplantation; D002540:Cerebral Cortex / Q000601:surgery*; D006801:Humans; D049449:Luminescence; D008855:Microscopy, Electron, Scanning; D058953:Neural Stem Cells / Q000166:cytology*; D051381:Rats; D054457:Tissue Scaffolds; D019076:Transgenes
chemical_list: D001672:Biocompatible Materials