机构:[1]PLA, Gen Hosp Beijing Mil Reg, Affiliated Bayi Brain Hosp, Beijing 100700, Peoples R China;[2]Neurosurg Inst Beijing Mil Reg, Beijing 100700, Peoples R China;[3]Third Mil Med Univ, Chongqing 400038, Peoples R China;[4]Anhui Med Univ, Hefei 230032, Peoples R China;[5]So Med Univ, Guangzhou 510515, Guangdong, Peoples R China;[6]Beijing Tiantan Hosp, Beijing 100050, Peoples R China;首都医科大学附属天坛医院[7]Natl Inst Biol Sci, Beijing 102206, Peoples R China;[8]Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
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.
基金:
China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2013M532138]; Military Twelfth Five-Year Key Sci-Tech Research Projects [BWS11J002, BWS12J010]; Gillson Longenbaugh Foundation
第一作者机构:[1]PLA, Gen Hosp Beijing Mil Reg, Affiliated Bayi Brain Hosp, Beijing 100700, Peoples R China;[2]Neurosurg Inst Beijing Mil Reg, Beijing 100700, Peoples R China;
通讯作者:
通讯机构:[1]PLA, Gen Hosp Beijing Mil Reg, Affiliated Bayi Brain Hosp, Beijing 100700, Peoples R China;[2]Neurosurg Inst Beijing Mil Reg, Beijing 100700, Peoples R China;
推荐引用方式(GB/T 7714):
Yao Hui,Gao Mou,Ma Jianhua,et al.Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats[J].PLOS ONE.2015,10(9):-.doi:10.1371/journal.pone.0137211.