In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury

Tai, Wenjiao; Wu, Wei; Wang, Lei Lei; Ni, Haoqi; Chen, Chunhai; Yang, Jianjing; Zang, Tong; Zou, Yuhua; Xu, Xiao Ming; Zhang, Chun Li

doi:10.1016/j.stem.2021.02.009

Cited by 121 publications

(135 citation statements)

References 63 publications

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“…Previous studies have shown that CTGF can stimulate glial scar formation by mediating downstream related proteins, such as vimentin, fibronectin, and laminin [12,13]. Vimentin is the intermediate filament of protein family, mainly in human glial cells, once the central nervous system is injured, vimentin will be significantly expressed [28,29]. In particular, vimentin can play an important role in the formation of glial scar tissue.…”

Section: Discussionmentioning

confidence: 99%

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Huang

et al. 2021

Stem Cell Res Ther

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Background How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. Methods We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, Results In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). Conclusions In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

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Section: Discussionmentioning

confidence: 99%

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Huang

et al. 2021

Stem Cell Res Ther

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“…Moreover, the in vivo regeneration of GABAergic neurons from astrocytes in Huntington’s disease mouse models can be achieved by AAV-mediated NeuroD1 and Dlx2 delivery [ 126 ]. Similarly, in Alzheimer’s disease models, reactive glial cells can be reprogrammed into functional glutamatergic or GABAergic neurons by retroviral expression of NeuroD1 [ 127 ]. As mentioned above, in Parkinson’s disease mouse models, direct reprogramming astrocytes into dopaminergic neurons through depleting Ptbp1 improves Parkinson’s disease-like motor phenotypes [ 82 , 128 ].…”

Section: Similarity In Brain Neural Regenerationmentioning

confidence: 99%

Advances in Regeneration of Retinal Ganglion Cells and Optic Nerves

Yuan

Wang

Jin

et al. 2021

IJMS

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Glaucoma, the second leading cause of blindness worldwide, is an incurable neurodegenerative disorder due to the dysfunction of retinal ganglion cells (RGCs). RGCs function as the only output neurons conveying the detected light information from the retina to the brain, which is a bottleneck of vision formation. RGCs in mammals cannot regenerate if injured, and RGC subtypes differ dramatically in their ability to survive and regenerate after injury. Recently, novel RGC subtypes and markers have been uncovered in succession. Meanwhile, apart from great advances in RGC axon regeneration, some degree of experimental RGC regeneration has been achieved by the in vitro differentiation of embryonic stem cells and induced pluripotent stem cells or in vivo somatic cell reprogramming, which provides insights into the future therapy of myriad neurodegenerative disorders. Further approaches to the combination of different factors will be necessary to develop efficacious future therapeutic strategies to promote ultimate axon and RGC regeneration and functional vision recovery following injury.

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“…Both NG2+ cells and ependymal cells have been reported to contribute to the formation of the scar border. More recently, NG2+ cells have shown to contribute to the generation of neurons in the injured spinal cord [44,46]. We will discuss the heterogeneity of NSPCs after injury with a focus on the activity of NG2+ and ependymal cells in Section 4.…”

Section: Adult Npscs In the Spinal Cordmentioning

confidence: 99%

“…The stem cell behavior of these populations has been implicated in the injury response and neurodegenerative/demyelinating disorders [71]. These populations are primarily glial producing cells; however, extrinsic and intrinsic factors have been used to modulate the glial fate to neuronal fate for functional recovery after traumatic injury [46,67]. Both populations have also been polemically associated with the glial scar formation after TBI and SCI in mammals [72,73].…”

Section: Controversial Nspc Populations In Injury/diseasementioning

confidence: 99%

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Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Finkel

Esteban

Rodriguez

et al. 2021

Preprint

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Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

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In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury

Cited by 121 publications

References 63 publications

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Advances in Regeneration of Retinal Ganglion Cells and Optic Nerves

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

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