Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy.
Bone marrow mesenchymal stem cells (BMSCs) hold a great promising approach for the treatment of epilepsy owing to their distinctive characteristics and multi-potency. However, there is little research focusing on the multi-potency of BMSCs in the treatment of epilepsy, the present study was designed to examine the influence of genetically engineered BMSCs (GE-BMSCs) on the functional outcome in a rat model of epilepsy. First, Hes1 gene of BMSCs was genetically engineered by RNA interference (RNAi), and then the GABAergic differentiation of GE-BMSCs was tested in vitro. Second, the lithium chloride-pilocarpine induced epileptic rats were administrated with the GE-BMSCs, the behavioral observation and electroencephalography (EEG) monitoring was employed to analyze the functional outcome on the epileptic model at different time points (day 7, day 14, day 21 and day 28), followed by histological verification. In vitro test showed that Hes1 silencing could promote BMSCs to differentiate into GABAergic neuron-like cells. In vivo test showed that GE-BMSCs graft could further improve the functional recovery of the epileptic rats, and the GABAergic differentiation of grafted GE-BMSCs was correlated with the functional recovery. Taken together, these data suggest that GE-BMSCs can improve the functional outcome in a rat model of epilepsy.
Department of Neurosurgery, The Central Hospital of Xi'an, Affiliated Hospital of Medical College of Xi'an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi'an 710003, China; Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, No. 17 Chang-le West Road, Xi'an 710032, China.
Qianfa
Q
Long
Bensheng
B
Qiu
Kai
K
Wang
Junle
J
Yang
Chenguang
C
Jia
Weichuan
W
Xin
Ping
P
Wang
Rui
R
Han
Zhou
Z
Fei
Weiping
W
Liu
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D059330:GABAergic Neurons / Q000166:cytology*; D005818:Genetic Engineering / Q000379:methods; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072056:Transcription Factor HES-1; D016896:Treatment Outcome
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat
Bone marrow mesenchymal stem cell; Epilepsy; Hes1; RNAi