Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity

Teng, Yun; Chen, Zhengsheng; Luo, Lei; Gao, Renzhi; Gong, Li; Du, Yukou; Xie, Zongping; Zhao, Bin; Li, Qing; Wang, Yan

doi:10.1016/j.bioactmat.2022.08.007

Cited by 19 publications

(50 citation statements)

References 54 publications

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“…It is found in liver injury research that, MAPK is activated in liver reperfusion injury [ 10 , 11 ]. Meanwhile, MAPK can activate the inflammatory response to exert its action [ 12 ], among which, tumor necrosis factor (TNF), adhesion molecule and NO have important effects [ 13 ]. At present, MAPK3 and MAPK1 are the subunit proteins with wide actions.…”

Section: Discussionmentioning

confidence: 99%

Triterpene acid from Antrodia camphorata alleviates inflammation in acute liver injury

Cao

Zhong

Chen

et al. 2023

Aging

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This study aimed to investigate the role and mechanism of Anctin A, the Antrodia camphorata terpene component, in resisting liver injury. Network pharmacology analysis revealed that MAPK3 was the major action target of Antcin A. Furthermore, experimental research suggested that Antcin A suppressed mouse liver injury, reduced the inflammatory factor levels, and enhanced the anti-oxidative capacity. Meanwhile, it suppressed the expression of MAPK3 and the downstream NF-κB signal, while it did not significantly affect the expression of MAPK1. Based on network pharmacology method, this study discovers that the anti-liver injury effect of Antcin A is mainly related to MAPK3, and that Antcin A can suppress the activation of MAPK3 and its downstream NF-κB to inhibit mouse ALI.

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Section: Discussionmentioning

confidence: 99%

Triterpene acid from Antrodia camphorata alleviates inflammation in acute liver injury

Cao

Zhong

Chen

et al. 2023

Aging

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“…An activator of the p38 pathway (U46619) was used to promote the phosphorylation of p38. [ 51 ] In the presence of U46619, the level of p‐p38 increased in the EVs Con group, whereas little alteration was observed in the EVs TIM3OE group (Figure 4G). The difference between the two groups demonstrated that the overexpression of TIM3 in macrophages caused by EVs TIM3OE could efficiently inhibit the activation of the p38/MAPK pathway.…”

Section: Resultsmentioning

confidence: 99%

“…[ 73–75 ] Studies have shown that IMSC‐derived EVs partially mediate the p38/MAPK signaling pathway and polarize M1 macrophages to M2 macrophages, thereby reducing pain and inflammation in tendon lesions. [ 51 ] In the subsequent mechanism exploration stage, through analysis and verification of transcriptome sequencing results, we found that TIM3 in EVs entered macrophages, activated the BMP2 promoter by inhibiting the p38/MAPK pathway, and released BMP2 cytokines to promote osseointegration. However, the potential participation of other pathways cannot be ruled out, and further studies are required.…”

Section: Discussionmentioning

confidence: 99%

Early‐Responsive Immunoregulation Therapy Improved Microenvironment for Bone Regeneration Via Engineered Extracellular Vesicles

Lu,

Liu,

Huang

et al. 2023

Adv Healthcare Materials

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Overactivated inflammatory reactions hinder the bone regeneration process. Timely transformation of microenvironment from pro‐inflammatory to anti‐inflammatory after acute immune response is favorable for osteogenesis. Macrophages play an important role in the immune response to inflammation. Therefore, this study adopts TIM3 high expression extracellular vesicles (EVs) with immunosuppressive function to reshape the early immune microenvironment of bone injury, mainly by targeting macrophages. These EVs can be phagocytosed by macrophages, thereby increasing the infiltration of TIM3‐positive macrophages (TIM3+ macrophages) and M2 subtypes. The TIM3+ macrophage group has some characteristics of M2 macrophages and secretes cytokines, such as IL‐10 and TGF‐β1 to regulate inflammation. TIM3, which is highly expressed in the engineered EVs, mediates the release of anti‐inflammatory cytokines by inhibiting the p38/MAPK pathway and promotes osseointegration by activating the Bmp2 promoter to enhance macrophage BMP2 secretion. After evenly loading the engineered EVs into the hydrogel, the continuous and slow release of EVsTIM3OE recruits more anti‐inflammatory macrophages during the early stages of bone defect repair, regulating the immune microenvironment and eliminating the adverse effects of excessive inflammation. In summary, this study provides a new strategy for the treatment of refractory wounds through early inflammation control.

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“…41 Large extracellular vesicles (LEVs) secreted by human induced pluripotent stem cells (iPSCs)-derived MSCs could ameliorate tendinopathy by regulating macrophage heterogeneity. 103 eMSCs are at the core of the theory of AM stem cell physiology and have gradually become a trending topic in the field of AM research. 104 However, the effect of eMSCs-derived EVs on the polarization of AAMs has not been reported, and this theory remains to be confirmed.…”

Section: The Molecular Mechanism Of Aam Polarizationmentioning

confidence: 99%

“…Recent studies indicated that exosomal miRNA‐124‐3p derived from BMSCs can alleviate nerve damage by promoting macrophage polarization to M2 41 . Large extracellular vesicles (LEVs) secreted by human induced pluripotent stem cells (iPSCs)‐derived MSCs could ameliorate tendinopathy by regulating macrophage heterogeneity 103 . eMSCs are at the core of the theory of AM stem cell physiology and have gradually become a trending topic in the field of AM research 104 .…”

Section: The Molecular Mechanism Of Aam Polarizationmentioning

confidence: 99%

Macrophage polarization in adenomyosis: A review

Qiu,

Cao,

et al. 2024

American J Rep Immunol

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Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis‐associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

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Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity

Cited by 19 publications

References 54 publications

Triterpene acid from Antrodia camphorata alleviates inflammation in acute liver injury

Triterpene acid from Antrodia camphorata alleviates inflammation in acute liver injury

Early‐Responsive Immunoregulation Therapy Improved Microenvironment for Bone Regeneration Via Engineered Extracellular Vesicles

Macrophage polarization in adenomyosis: A review

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