Home >> Neurological Research, Volume 31, Number 9

Effects of human neural stem cell transplantation in canine spinal cord hemisection

Authors: Lee, Seung-Hoon1; Chung, You-Nam2; Kim, Yoon-Ha1; Kim, Young-Ju1; Park, Jong-Pil2; Kwon, Dae-Kee3; Kwon, Oh-Seo3; Heo, Jae-Hyeok1; Kim, Yoon-Hee1; Ryu, Sun1; Kang, Hyo-Jin2; Paek, Sun Ha2; Wang, Kyu-Chang4; Kim, Seung5; Yoon, Byung-Woo1

Source: Neurological Research, Volume 31, Number 9, November 2009 , pp. 996-1002(7)

Publisher: Maney Publishing

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Abstract:

Objectives: Previous works have reported that the transplantation of neural stem cells (NSCs) may improve functional recovery after spinal cord injury (SCI), but these results have been mainly obtained in rat models. In the present work, the authors sought to determine whether the transplantation of human NSCs improves functional outcome in a canine SCI model and whether transplanted NSCs survive and differentiate.

Methods: Human NSCs (HB1. F3 clone) were used in this work. Lateral hemisection at the L2 level was performed in dogs and either (1) Matrigel (200 ?l) alone as a growth-promoting matrix or (2) Matrigel seeded with human NSCs (107 cells/200 ?l) were transplanted into hemisected gaps. Using a canine hind limb locomotor scale, functional outcomes were assessed over 12 weeks. Immunofluorescence staining was performed to examine cell survival, differentiation and axonal regeneration.

Results: Compared with dogs treated with Matrigel alone, dogs treated with Matrigel + human NSCs showed significantly better functional recovery (10.3 ? 0.7 versus 15.6 ? 0.7, respectively, at 12 weeks; p<0.05). Human nuclei-positive cells were found mainly near hemisected areas in dogs treated with Matrigel + NSCs. In addition, colocalization of human nuclei and neuronal nuclei or myelin basic protein was clearly observed. Moreover, the Matrigel + NSC group showed more ascending sensory axon regeneration.

Conclusions: The transplantation of human NSCs has beneficial effects on functional recovery after SCI, and these NSCs were found to differentiate into mature neurons and/or oligodendrocytes. These results provide baseline data for future clinical applications.Objectives: Previous works have reported that the transplantation of neural stem cells (NSCs) may improve functional recovery after spinal cord injury (SCI), but these results have been mainly obtained in rat models. In the present work, the authors sought to determine whether the transplantation of human NSCs improves functional outcome in a canine SCI model and whether transplanted NSCs survive and differentiate.

Methods: Human NSCs (HB1. F3 clone) were used in this work. Lateral hemisection at the L2 level was performed in dogs and either (1) Matrigel (200 ?l) alone as a growth-promoting matrix or (2) Matrigel seeded with human NSCs (107 cells/200 ?l) were transplanted into hemisected gaps. Using a canine hind limb locomotor scale, functional outcomes were assessed over 12 weeks. Immunofluorescence staining was performed to examine cell survival, differentiation and axonal regeneration.

Results: Compared with dogs treated with Matrigel alone, dogs treated with Matrigel + human NSCs showed significantly better functional recovery (10.3 ? 0.7 versus 15.6 ? 0.7, respectively, at 12 weeks; p<0.05). Human nuclei-positive cells were found mainly near hemisected areas in dogs treated with Matrigel + NSCs. In addition, colocalization of human nuclei and neuronal nuclei or myelin basic protein was clearly observed. Moreover, the Matrigel + NSC group showed more ascending sensory axon regeneration.

Conclusions: The transplantation of human NSCs has beneficial effects on functional recovery after SCI, and these NSCs were found to differentiate into mature neurons and/or oligodendrocytes. These results provide baseline data for future clinical applications.

Keywords: NEURAL STEM CELL; SPINAL CORD INJURY; DOG

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/174313209X385626

Affiliations: 1: Department of Neurology, Seoul National University and Seoul National University Hospital, Seoul, Korea; Neuroscience Research Center, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea 2: Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea 3: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea 4: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea 5: Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea; Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, Canada

Publication date: 2009-11-01

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