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Combination of multifaceted strategies to maximize the therapeutic benefits of neural stem cell transplantation for spinal cord repair.

Authors
Hwang, DH; Kim, HM; Kang, YM; Joo, IS; Cho, CS; Yoon, BW; Kim, SU; Kim, BG
Citation
Cell transplantation, 20(9):1361-1379, 2011
Journal Title
Cell transplantation
ISSN
0963-68971555-3892
Abstract
Neural stem cells (NSCs) possess therapeutic potentials to reverse complex pathological processes following spinal cord injury (SCI), but many obstacles remain that could not be fully overcome by NSC transplantation alone. Combining complementary strategies might be required to advance NSC-based treatments to the clinical stage. The present study was undertaken to examine whether combination of NSCs, polymer scaffolds, neurotrophin-3 (NT3), and chondroitinase, which cleaves chondroitin sulfate proteoglycans at the interface between spinal cord and implanted scaffold, could provide additive therapeutic benefits. In a rat hemisection model, poly(ɛ-caprolactone) (PCL) was used as a bridging scaffold and as a vehicle for NSC delivery. The PCL scaffolds seeded with F3 NSCs or NT3 overexpressing F3 cells (F3.NT3) were implanted into hemisected cavities. F3.NT3 showed better survival and migration, and more frequently differentiated into neurons and oligodendrocytes than F3 cells. Animals with PCL scaffold containing F3.NT3 cells showed the best locomotor recovery, and motor evoked potentials (MEPs) following transcranial magnetic stimulation were recorded only in PCL-F3.NT3 group in contralateral, but not ipsilateral, hindlimbs. Implantation of PCL scaffold with F3.NT3 cells increased NT3 levels, promoted neuroplasticity, and enhanced remyelination of contralateral white matter. Combining chondroitinase treatment after PCL-F3.NT3 implantation further enhanced cell migration and promoted axonal remodeling, and this was accompanied by augmented locomotor recovery and restoration of MEPs in ipsilateral hindlimbs. We demonstrate that combining multifaceted strategies can maximize the therapeutic benefits of NSC transplantation for SCI. Our results may have important clinical implications for the design of future NSC-based strategies.
MeSH terms
AnimalsAxons/drug effects/metabolismBehavior, Animal/drug effectsCell Differentiation/drug effectsCell LineCell Movement/drug effectsCell Survival/drug effectsChondroitin Sulfate Proteoglycans/metabolismCombined Modality TherapyEvoked Potentials, Motor/drug effectsFemaleHumansMiceMotor Activity/drug effectsNeural Stem Cells/cytology/*transplantation/ultrastructureNeurotrophin 3/pharmacologyPhenotypePolyesters/pharmacologyRatsRats, Sprague-DawleyRecovery of Function/drug effectsSpinal Cord/drug effects/pathology/physiopathology/surgery*Spinal Cord Regeneration/drug effects*Stem Cell TransplantationTissue Scaffolds/chemistry
DOI
10.3727/096368910X557155
PMID
21396156
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
황, 동훈주, 인수김, 병곤
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