Abstract
IntroductionStem cells have been evaluated as a potential therapeutic approach for several neurological disorders of the central and peripheral nervous system as well as for traumatic brain and spinal cord injury. Currently, the lack of a reliable and safe method to accurately and non-invasively locate the site of implantation and track the migration of stem cells in vivo hampers the development of stem cell therapy and its clinical application.In this report, we present data that demonstrate the feasibility of using the human sodium iodide symporter (hNIS) as a reporter gene for tracking neural stem cells (NSCs) after transplantation in the brain by using single-photon emission tomography/computed tomography (SPECT/CT) imaging.MethodsNSCs were isolated from the hippocampus of adult rats (Hipp-NSCs) and transduced with a lentiviral vector containing the hNIS gene. Hipp-NSCs expressing the hNIS (NIS-Hipp-NSCs) were characterized in vitro and in vivo after transplantation in the rat brain and imaged by using technetium-99m (99mTc) and a small rodent SPECT/CT apparatus. Comparisons were made between Hipp-NSCs and NIS-Hipp-NSCs, and statistical analysis was performed by using two-tailed Student’s t test.ResultsOur results show that the expression of the hNIS allows the repeated visualization of NSCs in vivo in the brain by using SPECT/CT imaging and does not affect the ability of Hipp-NSCs to generate neuronal and glial cells in vitro and in vivo.ConclusionsThese data support the use of the hNIS as a reporter gene for non-invasive imaging of NSCs in the brain. The repeated, non-invasive tracking of implanted cells will accelerate the development of effective stem cell therapies for traumatic brain injury and other types of central nervous system injury.
Highlights
Stem cells have been evaluated as a potential therapeutic approach for several neurological disorders of the central and peripheral nervous system as well as for traumatic brain and spinal cord injury
Expansion and characterization of Hipp-Neural stem cell (NSC) NSCs were isolated from the hippocampus of adult rats and maintained in culture in serum-free neurobasal A medium supplemented with B27 and the growth factors Epidermal growth factor (EGF) and Fibroblast growth factor-2 (FGF-2)
When Hipp-NSCs were plated onto poly-ornithine/ laminin-coated plates in serum-free medium containing B27, retinoic acid, and no growth factors (EGF and FGF2), they attached to the substrate and underwent rapid morphological changes (Fig. 1c)
Summary
Stem cells have been evaluated as a potential therapeutic approach for several neurological disorders of the central and peripheral nervous system as well as for traumatic brain and spinal cord injury. The lack of a reliable and safe method to accurately and non-invasively locate the site of implantation and track the migration of stem cells in vivo hampers the development of stem cell therapy and its clinical application. Several reports have explored the therapeutic potential of neural stem cells (NSCs) for the treatment of neurological disorders of the central nervous system (CNS) (i.e., macular degeneration, Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis) and for traumatic brain and spinal cord injury [1,2,3,4,5,6,7,8]. The successful development of stem cell therapy and its translation to the clinical setting is currently hampered by the lack of a reliable and safe method to accurately monitor the location, migration, and phenotypical differentiation of transplanted cells. PET has the ability to detect reporter genes [10, 11]
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