Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells.
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Neurosurgery Institute of Beijing Military Region, Beijing, 100700, PR China.
Hui
H
Yao
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; The Third Military Medical University, Chongqing, 400038, PR China.
Mou
M
Gao
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Anhui Medical University, Hefei, 230032, PR China.
Jianhua
J
Ma
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Southern Medical University, Guangzhou, 510515, PR China.
Maoying
M
Zhang
Beijing Tiantan Hospital, Beijing, 100050, PR China.
Shaowu
S
Li
Anhui Medical University, Hefei, 230032, PR China.
Bingshan
B
Wu
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Southern Medical University, Guangzhou, 510515, PR China.
Xiaohu
X
Nie
National Institute of Biological Science, Beijing, 102206, PR China.
Jiao
J
Jiao
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Neurosurgery Institute of Beijing Military Region, Beijing, 100700, PR China.
Hao
H
Zhao
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Neurosurgery Institute of Beijing Military Region, Beijing, 100700, PR China.
Shanshan
S
Wang
National Institute of Biological Science, Beijing, 102206, PR China.
Yuanyuan
Y
Yang
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Anhui Medical University, Hefei, 230032, PR China.
Yesen
Y
Zhang
Beijing Tiantan Hospital, Beijing, 100050, PR China.
Yilin
Y
Sun
University of Michigan, Comprehensive Cancer Center, Ann Arbor, Michigan, 48109, United States f of America.
Max S
MS
Wicha
University of Michigan, Comprehensive Cancer Center, Ann Arbor, Michigan, 48109, United States f of America.
Alfred E
AE
Chang
National Institute of Biological Science, Beijing, 102206, PR China.
Shaorong
S
Gao
University of Michigan, Comprehensive Cancer Center, Ann Arbor, Michigan, 48109, United States f of America.
Qiao
Q
Li
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, P.L.A, Beijing, 100700, PR China; Neurosurgery Institute of Beijing Military Region, Beijing, 100700, PR China.
Ruxiang
R
Xu
D000818:Animals; D001253:Astrocytes / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics; D054338:Cell Transdifferentiation; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D009474:Neurons / Q000637:transplantation; D009836:Oligodendroglia / Q000637:transplantation; D051381:Rats