22 306

Cited 28 times in

Overexpression of Bcl-XL in human neural stem cells promotes graft survival and functional recovery following transplantation in spinal cord injury.

Authors
Lee, SI; Kim, BG; Hwang, DH; Kim, HM; Kim, SU
Citation
Journal of neuroscience research, 87(14):3186-3197, 2009
Journal Title
Journal of neuroscience research
ISSN
0360-40121097-4547
Abstract
Transplantation of neural stem cells (NSCs) has shown promise for improving functional recovery after spinal cord injury (SCI). The inhospitable milieu of injured spinal cord, however, does not support survival of grafted NSCs, reducing therapeutic efficacy of transplantation. The present study sought to examine whether overexpression of antiapoptotic gene Bcl-X(L) in NSCs could promote graft survival and functional recovery following transplantation in rat contusive SCI model. A human NSC line (HB1.F3) was transduced with a retroviral vector encoding Bcl-X(L) to generate Bcl-X(L)-overexpressing NSCs (HB1.F3.Bcl-X(L)). Overexpression of Bcl-X(L) conferred resistance to staurosporine-mediated apoptosis. The number of HB1.F3.Bcl-X(L) cells was 1.5-fold higher at 2 weeks and 10-fold higher at 7 weeks posttransplantation than that of HB1.F3 cells. There was no decline in the number of HB1.F3.Bcl-X(L) cells between 2 and 7 weeks, indicating that Bcl-X(L) overexpression completely blocked cell death occurring between these two time points. Transplantation of HB1.F3.Bcl-X(L) cells improved locomotor scores and enhanced accuracy of hindlimb placement in a grid walk. Approximately 10% of surviving NSCs differentiated into oligodendrocytes. Surviving NSCs produced brain-derived neurotrophic factor (BDNF), and the level of BDNF was significantly increased only in the HB1.F3.Bcl-X(L) group. Transplantation of HB1.F3.Bcl-X(L) cells reduced cavity volumes and enhanced white matter sparing. Finally, HB1.F3.Bcl-X(L) grafts enhanced connectivity between the red nucleus and the spinal cord below the lesion. These results suggest that enhancing graft survival with antiapoptotic gene can potentiate therapeutic benefits of NSC-based therapy for SCI.
MeSH terms
AnimalsEnzyme-Linked Immunosorbent AssayFemaleGraft Survival/physiology*HumansNerve Regeneration/physiologyNeurons/metabolismNeurons/transplantation*RatsRats, Sprague-DawleyRecovery of Function/physiology*Spinal Cord Injuries/therapy*Stem Cell Transplantation/methodsStem Cells/cytologyTransfectionbcl-X Protein/biosynthesis*bcl-X Protein/genetics
DOI
10.1002/jnr.22149
PMID
19530162
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
AJOU Authors
이승임김병곤황동훈
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse