hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice

Kong, Desheng; Feng, Baofeng; Asiamah, Ernest Amponsah; He, Jingjing; Guo, Ruiyun; Liu, Boxin; Du, Xiaofeng; Liu, Xin; Zhang, Shuhan; Lv, Fei; Ma, Jun; Cui, Huixian

doi:10.1186/s13287-021-02217-9

Cited by 33 publications

(26 citation statements)

References 54 publications

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“…Then HE staining and Masson Trichrome staining (Boster, Wuhan, China) were performed after deparaffinization with xylene and hydration according to the manufacturer’s protocol. The images were taken under a light microscope [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation

Ban

Xiang

et al. 2022

Bioengineered

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Non-canonical signaling pathways have been proved to act as potent sites of astrocytes osmotic expanding or proliferation, which promotes the regeneration of axons in areas with non-neural spinal cord injury (SCI). However, the relevant signal pathway that induces autophagic cell death in astrocytes and its function relative to the TNF-like weak inducer of apoptosis/nuclear factor κB (TWEAK/NF-κB) axis remains elusive. The SCI model was established by vertically striking the spinal cord according to Allen’s model. Astrocytes and neuronal cells were prepared from spinal cells extracted from spinal cord tissues of SCI or normal C57BL/6 newborn mice. After co-culturing astrocytes and neurons, cell viability and autophagy were determined by CCK-8, transmission electron microscopy (TEM), and western blot. The expression of TWEAK, NF-κB and inflammatory cytokines was confirmed by qRT-PCR, western blot, Immunofluorescence and ELISA assay. Chromatin immunoprecipitation (CHIP) was used to evaluate the interaction between TWEAK and NF-κB. Our results demonstrated that knockdown of TWEAK and NF-κB inhibited secretion of high levels of TNF-α/IL-1β, partially counteracted by adding Rap. TWEAK/NF-κB was the positive correlation feedback loop regulating the proliferation and autophagy of astrocytes involved in SCI. Moreover, restraining the excess growth of astrocytes was beneficial to the growth of neurons. Collectively, our findings illustrated that the TWEAK/NF-κB pathway might act as a positive modulator of SCI by inducing astrocyte activation, shedding new insights for SCI treatment.

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Section: Methodsmentioning

confidence: 99%

TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation

Ban

Xiang

et al. 2022

Bioengineered

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“…Another translational concern is the risk of immune rejection, and therefore the use of immunosuppressants, since NSPCs are most commonly derived from embryonic stem cells or allogeneic adult sources [22], and human NSPCs with time in culture will increase their Major Histocompatibility Complex Class I and II expressions [23]. The induced pluripotent stem cell (iPSC)-derived and directly reprogrammed NSCs have offered the possibility of autologous transplantation, which mitigates immune rejection concerns [24,25]. However, even for autologous iPSC transplantation, there is a chance of triggering an immune response.…”

Section: Neural Stem/progenitor Cellsmentioning

confidence: 99%

Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Guo

Redenski

Levenberg

2021

Cells

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Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.

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“…Various iPSC-derived NSCs were grafted into the injured spinal cord, and considerable information has been gained about their survival, proliferation and differentiation capacity, as well as their migration properties [108,[113][114][115][116][117]. Tsuji et al established various mouse iPSC lines by different methods and detailed an evaluation of the cells, including their differentiation potential and tumorigenic activities.…”

Section: Delivery Of Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Stem Cell Secretome for Spinal Cord Repair: Is It More than Just a Random Baseline Set of Factors?

Pajer¹,

Bellák²,

Nógrádi³

2021

Cells

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Hundreds of thousands of people suffer spinal cord injuries each year. The experimental application of stem cells following spinal cord injury has opened a new era to promote neuroprotection and neuroregeneration of damaged tissue. Currently, there is great interest in the intravenous administration of the secretome produced by mesenchymal stem cells in acute or subacute spinal cord injuries. However, it is important to highlight that undifferentiated neural stem cells and induced pluripotent stem cells are able to adapt to the damaged environment and produce the so-called lesion-induced secretome. This review article focuses on current research related to the secretome and the lesion-induced secretome and their roles in modulating spinal cord injury symptoms and functional recovery, emphasizing different compositions of the lesion-induced secretome in various models of spinal cord injury.

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hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice

Cited by 33 publications

References 54 publications

TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation

TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation

Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Stem Cell Secretome for Spinal Cord Repair: Is It More than Just a Random Baseline Set of Factors?

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