Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord.
Implantation of marrow-derived mesenchymal stem cells (MSCs) is the most promising therapeutic strategy for the treatment of spinal cord injury (SCI), especially because of their potential for clinical application, such as the avoidance of immunologic rejection, their strong secretory properties, and their plasticity for developing into neural cells. However, the recovery from SCI after MSC implantation is minimal due to their limited capacity for the reduction of cystic cavitation, for the axonal regeneration and their uncertain neural plasticity in the spinal cord. We previously pretreated MSCs with all-trans retinoic acid (RA) in vitro. Then we genetically modified them to overexpress neurotrophin-3 (NT-3) via a recombinant adenoviral vector (Adv). This combined treatment not only permitted more neuronal differentiation of MSCs, but stimulated more NT-3 secretion prior to grafting, according to our previous and present results. When these cells were implanted into the transected spinal cord of rats, the animals had some improvement (both functionally and structurally), including the recovery of hindlimb locomotor function, shown by the highest Basso, Beattie, and Bresnahan (BBB) scores, as well as dramatically reduced cavity volume, clear axonal regeneration and more neuronal survival. In contrast, simple MSC implantation is not a very effective therapy for spinal transection. However, the neuronal differentiation of MSCs after treatment with a combination of Adv-mediated NT-3 gene transfer and RA was only mildly improved in vivo.
Zhang
Wei
W
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangzhou, China.
Yan
Qing
Q
Zeng
Yuan-Shan
YS
Zhang
Xue-Bao
XB
Xiong
Yi
Y
Wang
Jun-Mei
JM
Chen
Shui-Jun
SJ
Li
Yan
Y
Bruce
Iain C
IC
Wu
Wutian
W
D000256:Adenoviridae / Q000235:genetics; D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics*; D020933:Neurotrophin 3 / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology / Q000601:surgery*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology
D020933:Neurotrophin 3; D014815:Vitamins; D014212:Tretinoin