Advances in immunotherapy for the treatment of spinal cord injury

Mamun, Abdullah Al; Monalisa, Ilma; Kubra, Khadija Tul; Akter, Afroza; Akter, Jaheda; Sarker, Tamanna; Munir, Fahad; Wu, Yanqing; Jia, Chang; Taniya, Masuma Afrin; Xiao, Jian

doi:10.1016/j.imbio.2020.152033

Cited by 25 publications

(13 citation statements)

References 188 publications

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“…Following the primary injury, ongoing pathological changes contribute to secondary injury, which is mainly characterized by chronic inflammation, cell dysfunction, vascular changes, etc. ( 6 ). Primary and secondary injury events not only activate resident astrocytes and microglia, fibroblasts, and other glial cells, but also contribute to the infiltration of peripheral immune cells, and the interaction between these cells underlies the glial scar, inflammation, ionic imbalance, and free radical formation, which together inhibit the formation of axonal regeneration and myelination ( Figure 1 ) ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Pang

Chen

et al. 2021

Front. Immunol.

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Transected axons are unable to regenerate after spinal cord injury (SCI). Glial scar is thought to be responsible for this failure. Regulating the formation of glial scar post-SCI may contribute to axonal regrow. Over the past few decades, studies have found that the interaction between immune cells at the damaged site results in a robust and persistent inflammatory response. Current therapy strategies focus primarily on the inhibition of subacute and chronic neuroinflammation after the acute inflammatory response was executed. Growing evidences have documented that mesenchymal stem cells (MSCs) engraftment can be served as a promising cell therapy for SCI. Numerous studies have shown that MSCs transplantation can inhibit the excessive glial scar formation as well as inflammatory response, thereby facilitating the anatomical and functional recovery. Here, we will review the effects of inflammatory response and glial scar formation in spinal cord injury and repair. The role of MSCs in regulating neuroinflammation and glial scar formation after SCI will be reviewed as well.

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Section: Introductionmentioning

confidence: 99%

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Pang

Chen

et al. 2021

Front. Immunol.

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“…The secondary injury plays a crucial role in SCI onset and progression, leading to acute and chronic inflammation, tissue architecture damage, and motor and sensory dysfunction ( Kong and Gao, 2017 ). Additionally, current research indicates that immune cell infiltration noticeably affects SCI development and progression ( Al Mamun et al, 2021 ). Therefore, this study aimed to discover relevant SCI biomarkers and to investigate the role of immune cell infiltration in SCI.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, it is necessary to elucidate the molecular mechanism by which diverse immune cells influence SCI progression. As previously stated, assessing immune cell infiltration and dissecting the components of invading immune cells is crucial for unraveling the SCI molecular system and identifying novel immunotherapeutic targets ( Ahmed et al, 2018 ; Al Mamun et al, 2021 ). CIBERSORT is a computational method for quantifying cell composition using gene expression data.…”

Section: Introductionmentioning

confidence: 99%

Revealing Potential Spinal Cord Injury Biomarkers and Immune Cell Infiltration Characteristics in Mice

Cao

2022

Front. Genet.

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Spinal cord injury (SCI) is a disabling condition with significant morbidity and mortality. Currently, no effective SCI treatment exists. This study aimed to identify potential biomarkers and characterize the properties of immune cell infiltration during this pathological event. To eliminate batch effects, we concurrently analyzed two mouse SCI datasets (GSE5296, GSE47681) from the GEO database. First, we identified differentially expressed genes (DEGs) using linear models for microarray data (LIMMA) and performed functional enrichment studies on those DEGs. Next, we employed bioinformatics and machine-learning methods to identify and define the characteristic genes of SCI. Finally, we validated them using immunofluorescence and qRT-PCR. Additionally, this study assessed the inflammatory status of SCI by identifying cell types using CIBERSORT. Furthermore, we investigated the link between key markers and infiltrating immune cells. In total, we identified 561 robust DEGs. We identified Rab20 and Klf6 as SCI-specific biomarkers and demonstrated their significance using qRT-PCR in the mouse model. According to the examination of immune cell infiltration, M0, M1, and M2 macrophages, along with naive CD8, dendritic cell-activated, and CD4 Follicular T cells may have a role in the progression of SCI. Therefore, Rab20 and Klf6 could be accessible targets for diagnosing and treating SCI. Moreover, as previously stated, immune cell infiltration may significantly impact the development and progression of SCI.

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“…Prolonged immune and inflammatory cascades contribute to secondary injury and impede neural regeneration. [ 143 ] Hence, regulating the activation of resident and recruited immune cells and modulating the immune microenvironments of SCI can reduce secondary injury and promote SCI repair and regeneration [ 144 ] ( Figure ). For example, anti‐inflammatory treatments, such as inhibiting the infiltration of neutrophils via specific immunodepleting, [ 145 ] or neutrophil decoys (neutrophil membrane‐coated nanoparticles), [ 146 ] blocked the extensive activation of monocytes, microglia, and astrocytes, reduced astroglial differentiation of NSCs, promoted neuronal survival, and thus significantly promoted functional recovery.…”

Section: Building a Regenerative Microenvironment For Sci Repairmentioning

confidence: 99%

Advances in Biomaterial‐Based Spinal Cord Injury Repair

Shen

Fan

You

et al. 2021

Adv Funct Materials

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Spinal cord injury (SCI) often leads to the loss of motor and sensory functions and is a major challenge in neurological clinical practice. Understanding the pathophysiological changes and the inhibitory microenvironment is crucial to enable the identification of potential mechanisms for functional restoration and to provide guidance for the development of efficient treatment and repair strategies. To date, the implantation of specifically functionalized biomaterials in the lesion area has been shown to help promote axon regeneration and facilitate neuronal circuit generation by remolding SCI microenvironments. Moreover, structural and functional restoration of the spinal cord through the transplantation of naive spinal cord tissue grafts from adult donors, artificial spinal cord-like tissue developed from tissue engineering, and 3D printing will open up new avenues for SCI treatment. This review focuses on the dynamic pathophysiological changes in SCI microenvironments, biomaterials for SCI repairs, strategies for restoring spinal cord structure and function, experimental animal models, regenerative mechanisms, and clinical studies for SCI repair. The current status, recent advances, challenges, and prospects of scaffold-based SCI repair from basic to clinical settings are summarized and discussed, to provide a reference that will help to guide the future exploration and development of spinal cord regeneration strategies.

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Advances in immunotherapy for the treatment of spinal cord injury

Cited by 25 publications

References 188 publications

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Revealing Potential Spinal Cord Injury Biomarkers and Immune Cell Infiltration Characteristics in Mice

Advances in Biomaterial‐Based Spinal Cord Injury Repair

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