Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

Yao, Hui; Gao, Mou; Ma, Jianhua; Zhang, Maoying; Li, Shaowu; Wu, Bingshan; Nie, Xiaohu; Jiao, Jiao; Zhao, Hao; Wang, Shanshan; Yang, Yuanyuan; Zhang, Yesen; Sun, Yilin; Wicha, Max S.; Chang, Alfred E.; Gao, Shaorong; Li, Qiao; Xu, Ran

doi:10.1371/journal.pone.0137211

Cited by 27 publications

(32 citation statements)

References 46 publications

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“…Hong et al transplanted mouse iNSCs into a rat model of spinal cord injury, next to the injured site. Despite both studies showing that iNSC transplantation has beneficial effects, the former and the latter detected mainly iNSC-derived astroglial cells [89] and neuronal cells in the MCAO rat brains [90], respectively, pointing toward different rescuing mechanisms. Mouse iNSCderived neurons extended their axons and formed synapses with host neurons and, already 4 weeks after transplantation, there were beneficial effects like immunomodulation, neural protection, and angiogenesis of the spinal cord.…”

Section: Functional Characterization Of Insc-derived Neuronsmentioning

confidence: 70%

“…Two weeks after transplantation, the authors found iNSC-derived astrocytes and oligodendrocytes in distinct brain areas with concomitant PLP formation [13]. Another study published in 2015 reported transplantation of mouse iNSCs into the brains of MCAO rats [90]. The iNSC-derived cells migrated and differentiated and, most importantly, restore damaged tissues reconstituting the local circuitry.…”

Section: Functional Characterization Of Insc-derived Neuronsmentioning

confidence: 99%

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Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

et al. 2019

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Second-generation reprogramming of somatic cells directly into the cell type of interest avoids induction of pluripotency and subsequent cumbersome differentiation procedures. Several recent studies have reported direct conversion of human somatic cells into stably proliferating induced neural stem cells (iNSCs). Importantly, iNSCs are easier, faster, and more cost-efficient to generate than induced pluripotent stem cells (iPSCs), and also have a higher level of clinical safety. Stably, self-renewing iNSCs can be derived from different cellular sources, such as skin fibroblasts and peripheral blood mononuclear cells, and readily differentiate into neuronal and glial lineages that are indistinguishable from their iPSC-derived counterparts or from NSCs isolated from primary tissues. This review focuses on the derivation and characterization of iNSCs and their biomedical applications. We first outline different approaches to generate iNSCs and then discuss the underlying molecular mechanisms. Finally, we summarize the preclinical validation of iNSCs to highlight that these cells are promising targets for disease modeling, autologous cell therapy, and precision medicine. Take the shortcut: from iPSC to iNSCForced expression of lineage-specific transcription factors (TFs) has been shown to reprogram the developmental potential of various somatic cell types e.g. by inducing pluripotency [1]. The seminal breakthrough of fibroblast reprogramming into iPSCs offers a novel experimental tool to generate patient-specific cells for developmental studies and diverse biomedical applications, such as disease modeling and cell therapy. Since then, efficiency and robustness of reprogramming protocols have been substantially improved, but the derivation of patient-specific iPSCs remains a lengthy and cumbersome procedure. Moreover, clinical applications require subsequent redifferentiation of iPSCs into the cell type of interest, which is inefficient and risky because transplanted undifferentiated iPSCs are tumorigenic. In the shadow of iPSC-type reprogramming, second-generation reprogramming paradigms have been developed to bypass the pluripotency state Abbreviations

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Section: Functional Characterization Of Insc-derived Neuronsmentioning

confidence: 70%

Section: Functional Characterization Of Insc-derived Neuronsmentioning

confidence: 99%

Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

et al. 2019

View full text Add to dashboard Cite

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“…NSCs have similar effects when transplanted into the cortical peri-infarct area 24 h after permanent MCAO (Chen et al, 2014; Zhang et al, 2009) or even when administered one week after MCAO (Chang et al, 2013b; Shen et al, 2010. Even NSCs derived from iPSCs can decrease apoptosis (Chang et al, 2013a; Yao et al, 2015). …”

Section: Putative Therapies For Enhancing Brain Self-repair and Strokmentioning

confidence: 99%

Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

Zhao

Willing

2018

Progress in Neurobiology

102

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Stroke represents a severe medical condition that causes stroke survivors to suffer from long-term and even lifelong disability. Over the past several decades, a vast majority of stroke research targets neuroprotection in the acute phase, while little work has been done to enhance stroke recovery at the later stage. Through reviewing current understanding of brain plasticity, stroke pathology, and emerging preclinical and clinical restorative approaches, this review aims to provide new insights to advance the research field for stroke recovery. Lifelong brain plasticity offers the long-lasting possibility to repair a stroke-damaged brain. Stroke impairs the structural and functional integrity of entire brain networks; the restorative approaches containing multi-components have great potential to maximize stroke recovery by rebuilding and normalizing the stroke-disrupted entire brain networks and brain functioning. The restorative window for stroke recovery is much longer than previously thought. The optimal time for brain repair appears to be at later stage of stroke rather than the earlier stage. It is expected that these new insights will advance our understanding of stroke recovery and assist in developing the next generation of restorative approaches for enhancing brain repair after stroke.

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“…B6 mouse GFP-expressing ESCs, iPSCs, iNSCs and NSCs were generated and cultured as described previously17. Detailed methods were provided in Supplementary Methods S2.…”

Section: Methodsmentioning

confidence: 99%

“…For example, embryonic stem cell (ESC), induced pluripotent stem cell (iPSC) and neural stem cell (NSC) grafts can exert beneficial effects on the restoration of cognition via cell replacement, trophic support and/or immune modulation after brain injury1516. Moreover, we previously reported that intracerebral transplantation of induced neural stem cells (iNSCs) generated directly from autologous somatic cells can promote neurological functional recovery in middle cerebral artery occlusion and CHI animals1718. Remarkably, we discovered that local iNSC grafts have the potential to modulate CNS inflammation following trauma.…”

mentioning

confidence: 99%

Systemic Administration of Induced Neural Stem Cells Regulates Complement Activation in Mouse Closed Head Injury Models

Gao

Dong

Yao³

et al. 2017

Sci Rep

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Complement activation plays important roles in the pathogenesis of central nervous system (CNS) diseases. Patients face neurological disorders due to the development of complement activation, which contributes to cell apoptosis, brain edema, blood-brain barrier dysfunction and inflammatory infiltration. We previously reported that induced neural stem cells (iNSCs) can promote neurological functional recovery in closed head injury (CHI) animals. Remarkably, we discovered that local iNSC grafts have the potential to modulate CNS inflammation post-CHI. In this study, we aimed to explore the role of systemically delivered iNSCs in complement activation following CNS injury. Our data showed that iNSC grafts decreased the levels of sera C3a and C5a and down-regulated the expression of C3d, C9, active Caspase-3 and Bax in the brain, kidney and lung tissues of CHI mice. Furthermore, iNSC grafts decreased the levels of C3d+/NeuN+, C5b-9+/NeuN+, C3d+/Map2+ and C5b-9+/Map2+ neurons in the injured cortices of CHI mice. Subsequently, we explored the mechanisms underlying these effects. With flow cytometry analysis, we observed a dramatic increase in complement receptor type 1-related protein y (Crry) expression in iNSCs after CHI mouse serum treatment. Moreover, both in vitro and in vivo loss-of-function studies revealed that iNSCs could modulate complement activation via Crry expression.

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Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

Cited by 27 publications

References 46 publications

Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

Systemic Administration of Induced Neural Stem Cells Regulates Complement Activation in Mouse Closed Head Injury Models

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