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.
Highlights
Traumatic brain injury (TBI), often defined as an acquired brain injury or a brain injury, is the leading cause of mortality and disability among young adults and elderly people, and it occurs when the brain is damaged by a sudden trauma such as those associated with falls, motor vehicle accidents, and surgical operations for epilepsy treatment [1,2]
Through in vivo bioluminescence imaging in motor-cortex-ablated rats, we investigated in vivo survival of human neural stem cells dependent on the mechanical support provided by biocompatible poly-L-lactic acid (PLLA) scaffolds
To establish genetically engineered F3 human neural stem cells for visualizing in vivo characteristics of the implanted stem cells, we used F3 neural stem cells stably expressing the codonoptimized enhanced firefly luciferase gene and a Thy1.1 (CD90.1) marker linked with internal ribosome entry site (IRES) under the control of the CMV promoter in the retroviral DNA backbone (Fig. 1A)
Summary
Traumatic brain injury (TBI), often defined as an acquired brain injury or a brain injury, is the leading cause of mortality and disability among young adults and elderly people, and it occurs when the brain is damaged by a sudden trauma such as those associated with falls, motor vehicle accidents, and surgical operations for epilepsy treatment [1,2]. Since the adult mammalian central nervous system (CNS) is limited in its capacity to utilize endogenous NSCs to repair neurologic deficits, cell replacement therapy can offer a potential means to recovery from the disability associated with neuronal loss. The severe conditions (oxidative stress, necrosis, inflammation) at the site of the injury are not favorable for the survival of grafted stem cells, limiting the effectiveness of stem cell therapy. To overcome this problem, a variety of methods for the introduction of neural stem cells that secrete growth factors, such as brain-derived neurotrophic factor (BDNF), have been investigated for the improvement of motor function in TBI models [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
