Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat.
Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone.
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.|Department of  Neurosurgery, Tongling Municipal Hospital, Tongling, 244000, Anhui, China.
Linjun
L
Tang
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Xiaocheng
X
Lu
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Ronglan
R
Zhu
Department of Neurosurgery, Jiangsu University Affiliated Jintan Hospital, Jintan, 213200, Jiangsu, China.
Tengda
T
Qian
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Yi
Y
Tao
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Kai
K
Li
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Jinyu
J
Zheng
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Penglai
P
Zhao
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Shuai
S
Li
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Xi
X
Wang
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. lilixin2@hotmail.com.
Lixin
L
Li
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C534807:Neurog2 protein, rat
Adipose-derived stem cells; Differentiation; Functional recovery; Neurogenin2; Spinal cord injury