Peer-Reviewed Journal Details
Mandatory Fields
Rooney, GE;McMahon, SS;Ritter, T;Garcia, Y;Moran, C;Madigan, NN;Flugel, A;Dockery, P;O'Brien, T;Howard, L;Windebank, AJ;Barry, FP
2009
October
Tissue Engineering Part A
Neurotrophic Factor-Expressing Mesenchymal Stem Cells Survive Transplantation into the Contused Spinal Cord Without Differentiating into Neural Cells
Published
WOS: 29 ()
Optional Fields
MARROW STROMAL CELLS NERVE GROWTH-FACTOR BONE-MARROW IN-VITRO AXONAL GROWTH ADULT-RAT BRAIN RECOVERY INJURY GDNF
15
3049
3059
The aim of this study was to assess the feasibility of transplanting mesenchymal stem cells (MSCs), genetically modified to express glial-derived neurotrophic factor (GDNF), to the contused rat spinal cord, and to subsequently assess their neural differentiation potential. MSCs expressing green fluorescent protein were transduced with a retroviral vector to express the neurotrophin GDNF. The transduction protocol was optimized by using green fluorescent protein-expressing retroviral constructs; approximately 90% of MSCs were transduced successfully after G418 selection. GDNF-transduced MSCs expressed the transgene and secreted growth factor into the media (similar to 12 ng/500,000 cells secreted into the supernatant 2 weeks after transduction). Injuries were established using an impactor device, which applied a given, reproducible force to the exposed spinal cord. GDNF-expressing MSCs were transplanted rostral and caudal to the site of injury. Spinal cord sections were analyzed 2 and 6 weeks after transplantation. We demonstrate that GDNF-transduced MSCs engraft, survive, and express the therapeutic gene up to 6 weeks posttransplantation, while maintaining an undifferentiated phenotype. In conclusion, transplanted MSCs have limited capacity for the replacement of neural cells lost as a result of a spinal cord trauma. However, they provide excellent opportunities for local delivery of neurotrophic factors into the injured tissue. This study underlines the therapeutic benefits associated with cell transplantation and provides a good example of the use of MSCs for gene delivery.
1937-3341
10.1089/ten.tea.2009.0045
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