Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury.
OBJECTIVE
Traumatic injury to the central nervous system (CNS) often causes motor dysfunctions. However, because of the CNS complexity and variability in the clinical presentations, efforts to repair damaged CNS tissue and restoring its functions are particularly demanding. On the other hand, recent progress in the regenerative therapy field have led to novel approaches for the treatment of traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that the balance between neurite re-growth-inhibiting and neurite re-growth-inducing molecules determines the axonal re-growth fate. Neurotrophic factors can tilt this balance and indeed promote cell survival and axonal re-growth over neurodegeneration. One of the promising neurotrophic factors in this field is ciliary neurotrophic factor (CNTF).


METHODS
We transfected rat bone marrow stromal cells with a mammalian expression vector-inserted human CNTF gene through the use of a non-viral method to prepare human CNTF-overexpressing stem cells under ex vivo conditions. We transplanted these modified cells to the rat model of spinal cord traumatic injury to explore functional recovery after contusion induction.


RESULTS
Our data from immunocytochemistry and behavioral tests showed that such cells can act as a powerful potential approach to treat traumatic CNS injuries because these modified cells improved the behavioral test scores in the rat model of spinal cord injury.


CONCLUSIONS
CNTF-overexpressing bone marrow stromal cells can ameliorate spinal cord traumatic injury and can be used in the treatment of traumatic CNS injuries in the near future.
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hojjat-Allah
HA
Abbaszadeh
Department of Anatomical Science, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Shefa Neuroscience Research Center, Khatam Al-Anbia Hospital, Tehran, Iran. Electronic address: takialtr@modares.ac.ir.
Taki
T
Tiraihi
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Ali
A
Noori-Zadeh
Department of Anatomical Science, School of Medical Science, Shahed University, Tehran, Iran.
Ali Reza
AR
Delshad
Department of Genetics, Faculty of Sciences, Tarbiat Modares University, Tehran, Iran.
Majid
M
Sadeghizade
Shefa Neuroscience Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.
Taher
T
Taheri
D000818:Animals; D001369:Axons / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003288:Contusions / Q000628:therapy; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000601:surgery; D013119:Spinal Cord Injuries / Q000628:therapy*; D014162:Transfection
D020934:Ciliary Neurotrophic Factor
BMSCs; CNS regeneration; CNS traumatic injury; CNTF