Use of engineered bone marrow stem cells to deliver brain derived neurotrophic factor under the control of a tetracycline sensitive response element in experimental allergic encephalomyelitis.
Brain derived neurotrophic factor (BDNF) has neuroprotective properties but its use has been limited by poor penetration of the blood brain barrier. Treatment using bone marrow stem cells (BMSC) or retroviruses as vectors reduces the clinical and pathological severity of experimental allergic encephalomyelitis (EAE). We have refined the BMSC based delivery system by introducing a tetracycline sensitive response element to control BDNF expression. We have now tested that construct in EAE and have shown a reduction in both the clinical and pathological severity of the disease. Further, we looked for changes in sirtuin1 and nicotinamide phosphoribosyltransferase expression that would be consistent with a neuroprotective effect.
VA Maryland Healthcare System, Baltimore, MD 21201, United States.
Tapas K
TK
Makar
Vamshi K C
VK
Nimmagadda
Gopi K
GK
Patibandla
Toby
T
Le
Susan I V
SI
Judge
David
D
Trisler
Christopher T
CT
Bever
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D020218:Response Elements / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology; D033581:Stem Cell Transplantation / Q000379:methods*; D013752:Tetracycline / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D013752:Tetracycline