Inhibition of TROY Promotes OPC Differentiation and Increases Therapeutic Efficacy of OPC Graft for Spinal Cord Injury

Sun, Liang; Liu, Shengliang; Sun, Qi; Li, Zhuying; Xu, Fanxing; Hou, Chunmei; Harada, Toshihide; Chu, Ming; Xu, Kun; Feng, Xiang; Duan, Yong-Shun; Zhang, Yafang; Wu, Shuliang

doi:10.1089/scd.2013.0563

Cited by 17 publications

(10 citation statements)

References 54 publications

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“…Moreover, the knockdown of Troy in situ transplantation of OPCs leads to notable demyelination and neurological recovery in rats with SCI. [34] Based on the described results, all of the NgR, LINGO-1, PTEN, and Troy are assured being involved in the axon injury during SCI which might interact with each other when neurons were damaged. In our study, we constructed a siRNA pool with results indicating that the expressions of axonal growth inhibitors were reduced remarkably with an increase of cell proliferation and alleviation of the Rho expression in primary spinal cord forms of SCI rats, thereby identifying a promising target mechanism of SCI by modifying the amount of axonal growth inhibitor.…”

Section: Discussionmentioning

confidence: 80%

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

Liao¹,

Ming²,

Guo³

2020

Preprint

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Background: As exosomes have been confirmed as a reservoir of siRNAs involved in certain diseases, the current study aims to investigate whether exosomal-siRNA could exert a protective role in spinal cord injury (SCI). Methods and Results: Exosomes in our experiment were isolated from lysosomal membrane-associated protein 2b (Lamp2b) overexpression HEK 293T cells, and purity of exosomes was characterized by the expression of CD9, CD47, and CD63 via western blot. Furthermore, the siRNA pool contains four siRNAs including siRNA-NgR, siRNA-LINGO-1, siRNA-Troy, and siRNA-PTEN was loaded to the exosomes, which indicated a significant role for the siRNA pool in reducing the expression of axon growth inhibitory factors. Upon the completion of loading into exosomes (exo-siRNA pool), the exo-siRNA pool was injected into primary cortical neurons of the SCI model in rats before cell proliferation and Rho expression were determined With the results revealed that purified addition could be applied to future experiments. The exo-siRNA pooled transfection caused downregulation of axon growth suppressors in primary cortical neurons including Nogo receptors (NgR), leucine-rich repeats and immunoglobulin domain-containing protein 1 (LINGO-1), Troy, and phosphatase and tenson homolog (PTEN). Cell proliferation and Rho expression of primary cortical neurons inhibited the expression of axonal growth inhibitors in rats with SCI by transfecting exogenous Sirna. Conclusion: This study confirmed that exosomes derived from Lamp2b overexpression HEK 293T cells facilitated both the recovery of functions and the survival of neurons when being loaded with the siRNA pool.

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Section: Discussionmentioning

confidence: 80%

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

Liao¹,

Ming²,

Guo³

2020

Preprint

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“…Bambakidis and Miller (2004) indicated that transplantation modestly improved functional recovery and spared white matter, but addition of recombinant sonic hedgehog (Shh) during cell transplantation failed to improve either outcome over OPC transplant alone. Knockdown of the TNF receptor TROY increased exogenous remyelination of grafted OPCs as well as hindlimb functional recovery post-injury (Sun et al, 2014). Cao et al (2010) confirmed the ensheathment and remyelination of grafted OPC-derived oligodendrocytes by immuno-EM and were able to correlate improvements in hindlimb function with improvements in oligodendrocyte remyelination by CNTF-expressing OPCs.…”

Section: Resultsmentioning

confidence: 99%

Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?

Myers

Bankston

Burke

et al. 2016

Experimental Neurology

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This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2,500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC). Of the NSPC/NPC/OPC grafts, there was no consistency with respect to the types of cells grafted and/or the additional growth factors or cells co-grafted. Enhanced functional recovery was reported in 31/45 studies, but only 20 of those had appropriate controls making conclusive interpretation of the remaining studies impossible. Of those 20, 19 were properly powered and utilized appropriate statistical analyses. Ten of those 19 studies reported the presence of graft-derived myelin, 3 reported evidence of endogenous remyelination or myelin sparing, and 2 reported both. For the SC grafts, 16/21 reported functional improvement, with 11 having appropriate cellular controls and 9/11 using proper statistical analyses. Of those 9, increased myelin was reported in 6 studies. The lack of consistency and replication among these preclinical studies are discussed with respect to the progression of myelinating cell transplantation therapies into the clinic.

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“…Western blotting was performed as described previously [ 21 , 22 ]. Briefly, cell samples were lysed in a buffer containing 10 mM Tris (pH 7.4), 100 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM NaF, 20 mM Na 4 P 2 O 7 , 2 mM Na 3 VO 4 , 0.1% SDS, 0.5% sodium deoxcholate, 1% Triton-X 100, 10% glycerol, 1 mM PMSF, 60 mg/mL aprotinin, 10 mg/mL leupeptin, and 1 mg/mL pepstatin.…”

Section: Methodsmentioning

confidence: 99%

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

Jie

Sun

et al. 2015

PLoS ONE

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Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

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Inhibition of TROY Promotes OPC Differentiation and Increases Therapeutic Efficacy of OPC Graft for Spinal Cord Injury

Cited by 17 publications

References 54 publications

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway

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