Transplantation of tauroursodeoxycholic acid–inducing M2‐phenotype macrophages promotes an anti‐neuroinflammatory effect and functional recovery after spinal cord injury in rats

Han, Gong Ho; Kim, Seong Jun; Ko, Wan‐Kyu; Lee, Daye; Han, Inbo; Sheen, Seung Hun; Hong, Jong Chul; Sohn, Seil

doi:10.1111/cpr.13050

Cited by 32 publications

(26 citation statements)

References 43 publications

(90 reference statements)

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“…M1 macrophages act as the bad guys by promoting inflammatory response, inhibiting axons regeneration and demyelination. In contrast, anti-inflammatory M2 macrophages play a protective role in promoting functional recovery by removing apoptotic cells and promoting axonal regeneration and myelin sheaths ( 48 , 49 ). During the process of skin and muscle wounds healing, macrophages will shift from M1 to M2 phenotype in response to the change of microenvironmental stimulus signals at the lesion site ( 50 , 51 ).…”

Section: Inflammatory Response After Scimentioning

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: Inflammatory Response After Scimentioning

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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“…To prove Mφ is detrimental Silica dust (Blight 1985) Exert cytotoxic effects to Mφ Less myelin axons and less vascularization in the lesion Clodronate (Popovich 1999) Deplete peripheral Mφ Decreased the tissue cavity and promoted motor function Anti-CD11d mAb (Gris 2004) Block the interaction between endothelial cell and hematogenous Mφ Increasing density of neurofilament axon Anti-αDβ2 mAb (Mabon 2000;Naeini et al, 2021) Block the connection of αDβ2-VCAM-1 Less necrotic debris and long-lasting sensorimotor function recovery Adiponectin Suppress myelin lipid accumulation Reduced myelin lipid accumulation and impaired neurogenesis To prove Mφ is beneficial C5a (Dander et al, 2021) Induce epicenter-directed macrophage migration Avoid neuron contact and reduce incidence of axonal dieback Transplantation (Han et al, 2021) Transfer…”

Section: Objective Treatment Experimental Principle Resultsmentioning

confidence: 99%

Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury

Ding

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Spinal cord injury (SCI) is a devastating disease leading to loss of sensory and motor functions, whose pathological process includes mechanical primary injury and secondary injury. Macrophages play an important role in SCI pathology. According to its origin, it can be divided into resident microglia and peripheral monocyte-derived macrophages (hematogenous Mφ). And it can also be divided into M1-type macrophages and M2-type macrophages on the basis of its functional characteristics. Hematogenous macrophages may contribute to the SCI process through infiltrating, scar forming, phagocytizing debris, and inducing inflammatory response. Although some of the activities of hematogenous macrophages are shown to be beneficial, the role of hematogenous macrophages in SCI remains controversial. In this review, following a brief introduction of hematogenous macrophages, we mainly focus on the function and the controversial role of hematogenous macrophages in SCI, and we propose that hematogenous macrophages may be a new therapeutic target for SCI.

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“…Vertebral column was supported and stabilized by clamps at the T7 and T11 spinous processes. A stainless-steel rod weighing 40 g (2.5 mm in diameter) was dropped from a height of 30.5 mm onto the dorsal surface of the spinal cord to induce injury using an impactor (RWD, CA, USA, Model: 68097) [ 30 ]. After the injury, the weight rod was quickly removed.…”

Section: Methodsmentioning

confidence: 99%

Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model

Kim

Han

et al. 2021

Pharmaceuticals

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Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.

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Transplantation of tauroursodeoxycholic acid–inducing M2‐phenotype macrophages promotes an anti‐neuroinflammatory effect and functional recovery after spinal cord injury in rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 32 publications

References 43 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

Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury

Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model

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