Effects of human neural stem cell transplantation in canine spinal cord hemisection.
OBJECTIVE
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 microl) alone as a growth-promoting matrix or (2) Matrigel seeded with human NSCs (10(7) cells/200 microl) 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.
Lee
Seung-Hoon
SH
Department of Neurology, Seoul National University and Seoul National University Hospital, Seoul, Korea.
Chung
You-Nam
YN
Kim
Yoon-Ha
YH
Kim
Young-Ju
YJ
Park
Jong-Pil
JP
Kwon
Dae-Kee
DK
Kwon
Oh-Seo
OS
Heo
Jae-Hyeok
JH
Kim
Yoon-Hee
YH
Ryu
Sun
S
Kang
Hyo-Jin
HJ
Paek
Sun Ha
SH
Wang
Kyu-Chang
KC
Kim
Seung U
SU
Yoon
Byung-Woo
BW
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology / Q000627:therapeutic use; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004285:Dogs; D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007797:Laminin / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D011509:Proteoglycans / Q000494:pharmacology / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D016896:Treatment Outcome
D034961:Antigens, Nuclear; D015415:Biomarkers; D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C506808:neuronal nuclear antigen NeuN, human; C059485:matrigel; D003094:Collagen; D015740:Calcitonin Gene-Related Peptide