Human Neural Stem Cell-Conditioned Medium Inhibits Inflammation in Macrophages Via Sirt-1 Signaling Pathway In Vitro and Promotes Sciatic Nerve Injury Recovery in Rats

Chen, Tianyan; Li, Yilei; Ni, Wei; Tang, Bin; Wei, Yu‐Sheng; Li, Jing; Yu, Jiahong; Zhang, Lei; Gao, Jianyi; Zhou, Jiqin; Zhang, Weining; Xu, He; Hu, Jiabo

doi:10.1089/scd.2020.0020

Cited by 27 publications

(16 citation statements)

References 38 publications

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“…Identifying a systemic benefit of the NSC secretome on immune system activation is an alluring premise. In rats with experimental sciatic nerve injury, which affects the peripheral nervous system, IV injection of CM from human embryo-derived NSCs provided promising results (Chen et al, 2020). Here, continual treatment with hNSC-CM in injured rats in vivo did not alter the acute, Schwann cell-driven inflammation, rather it abrogated the macrophage-driven inflammatory response in the chronic stage through a reduction in the expression of pro-inflammatory cytokines Tnf, Il6, and Il1b and the accumulation of CD68 + macrophages.…”

Section: Approaches For Studying the Nsc-secretome In Regenerative Nementioning

confidence: 99%

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Willis

Nicaise

Hamel

et al. 2020

Front. Cell. Neurosci.

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Increasing evidence foresees the secretome of neural stem cells (NSCs) to confer superimposable beneficial properties as exogenous NSC transplants in experimental treatments of traumas and diseases of the central nervous system (CNS). Naturally produced secretome biologics include membrane-free signaling molecules and extracellular membrane vesicles (EVs) capable of regulating broad functional responses. The development of high-throughput screening pipelines for the identification and validation of NSC secretome targets is still in early development. Encouraging results from pre-clinical animal models of disease have highlighted secretome-based (acellular) therapeutics as providing significant improvements in biochemical and behavioral measurements. Most of these responses are being hypothesized to be the result of modulating and promoting the restoration of key inflammatory and regenerative programs in the CNS. Here, we will review the most recent findings regarding the identification of NSC-secreted factors capable of modulating the immune response to promote the regeneration of the CNS in animal models of CNS trauma and inflammatory disease and discuss the increased interest to refine the pro-regenerative features of the NSC secretome into a clinically available therapy in the emerging field of Regenerative Neuroimmunology.

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Section: Approaches For Studying the Nsc-secretome In Regenerative Nementioning

confidence: 99%

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Willis

Nicaise

Hamel

et al. 2020

Front. Cell. Neurosci.

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“…A soft vs. stiff). The gait changes of the rats are accompanied by atrophy of the gastrocnemius muscle, so the wet weight and muscle fiber area of the gastrocnemius of different groups of rats were also analyzed ( Chen et al, 2020 ; Lopez-Silva et al, 2021 ; Singh et al, 2021 ). The results showed that sciatic nerve injury resulted in atrophy of the gastrocnemius muscle on the operating side, a decrease in wet weight, and a decrease in muscle fiber area ( Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

“…The 100% value of the wet gastrocnemius muscle weight on the operating side/wet gastrocnemius muscle weight on the normal side was used to evaluate gastrocnemius atrophy caused by sciatic nerve damage ( Singh et al, 2021 ). Moreover, the gastrocnemius muscle was cross-sectioned, and H&E staining analysis of the muscle fiber area was performed to further assess the level of muscle atrophy ( Chen et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Low-Stiffness Hydrogels Promote Peripheral Nerve Regeneration Through the Rapid Release of Exosomes

Liu¹,

Tong

et al. 2022

Front. Bioeng. Biotechnol.

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A hydrogel system loaded with mesenchymal stem cell–derived exosome (MSC-Exos) is an attractive new tool for tissue regeneration. However, the effect of the stiffness of exosome-loaded hydrogels on tissue regeneration is unclear. Here, the role of exosome-loaded hydrogel stiffness, during the regeneration of injured nerves, was assessed in vivo. The results showed that the photocrosslinkable hyaluronic acid methacrylate hydrogel stiffness plays an important role in repairing nerve injury. Compared with the stiff hydrogels loaded with exosomes, soft hydrogels loaded with exosomes showed better repair of injured peripheral nerves. The soft hydrogel promoted nerve repair by quickly releasing exosomes to inhibit the infiltration of macrophages and the expression of the proinflammatory factors IL-1β and TNF-α in injured nerves. Our work revealed that exosome-loaded hydrogel stiffness plays an important role in tissue regeneration by regulating exosome release behavior and provided important clues for the clinical application of biological scaffold materials.

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“…At 24 h after stroke modeling, the animals ( n = 34) were randomly attributed to 1 of the following 3 groups: the control group ( n = 10), which received intra-arterial infusions of the non-conditioned DMEM/F12-based medium; one group of CM recipients ( n = 12), which received intra-arterial infusions of GPC-CM (50 µg/mL of total protein); and another group of CM recipients ( n = 12), which received intra-arterial infusions of NPC-CM (50 µg/mL of total protein). The doses of GPC-CM and NPC-CM were chosen according to the literature data [ 38 , 39 ]. It is worth noting that the optimal “time window” for intra-arterial transplantation of stem/progenitor cells or their conditioned medium has not been firmly established yet [ 40 , 41 ].…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Salikhova

Бухарова

Cherkashova

et al. 2021

IJMS

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Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.

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Human Neural Stem Cell-Conditioned Medium Inhibits Inflammation in Macrophages Via Sirt-1 Signaling Pathway In Vitro and Promotes Sciatic Nerve Injury Recovery in Rats

Cited by 27 publications

References 38 publications

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Low-Stiffness Hydrogels Promote Peripheral Nerve Regeneration Through the Rapid Release of Exosomes

Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

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