Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

Ma, Ke; Zhu, Bo; Wang, Zetao; Cai, Peian; He, Mingwei; Ye, Danyan; Yan, Guohua; Zheng, Li; Yang, Lujun; Zhao, Jinmin

doi:10.21203/rs.3.rs-23463/v3

Cited by 7 publications

(9 citation statements)

References 31 publications

(37 reference statements)

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“…The fresh human umbilical cords were acquired under sterile conditions from healthy donors following full-term cesarean operation in The First Affiliated Hospital of Guangxi Medical University. Extraction of the MSCs from the human umbilical cords as described previously [ 48 ]. Briefly, the blood vessels in the umbilical cords are first removed and subsequently minced to obtain Wharton's jelly.…”

Section: Methodsmentioning

confidence: 99%

Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

et al. 2022

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Osteoarthritis (OA) is a degenerative illness that greatly impacts the life quality of patients. Currently, the therapeutic approaches for OA are very limited in clinical. The extracellular vesicles (EVs) derived from different mesenchymal stem cells displayed a prominent therapeutic effect on OA. But most EVs have limited resources and the risks of host rejection, immunological response, and etc. Human umbilical cord mesenchymal stem cells (hUCMSCs) hold the advantages of easy availability, minimal immune rejection, and excellent immunomodulatory effects, although hUCMSCs-EVs have seldom been applied in OA. Herein, we investigated the potential immunomodulatory and anti-inflammatory effects of hUCMSCs-EVs on the treatment of OA. In our results, the treatment of hUCMSCs-EVs promoted the polarization of M2-type macrophages and the expression of anti-inflammation-related cytokines (IL-10). Notably, the supernate of M2 macrophages induced by hUCMSCs-EVs inhibited the level of inflammation-associated factors in OA chondrocytes caused by IL-1β. Further, injection of hUCMSCs-EVs in the articular lumen ameliorated progression of OA and exerted chondroprotective potential based on the OA joint model created by the surgical transection of the anterior cruciate ligament (ACLT). In addition, we found five highly enriched miRNAs in hUCMSCs-EVs, including has-miR-122-5p, has-miR-148a-3p, has-miR-486-5p, has-miR-let-7a-5p, and has-miR-100-5p by High-throughput sequencing of miRNAs, with targeted genes mainly enriched in the PI3K-Akt signaling pathway. Furthermore, we also detected the protein abundance of hUCMSCs-EVs using liquidation chromatography with tandem quadrupole mass spectrometry (LC–MS/MS) analysis. Thus, our study indicates that hUCMSCs-EVs can alleviate cartilage degradation during the OA progression, mechanically may through delivering key proteins and modulating the PI3K-Akt signaling pathway mediated by miRNAs to promote polarization of M2 macrophage, exhibiting potent immunomodulatory potential. The current findings suggest that hUCMSCs-EVs might serve as a new reagent for the therapy of OA. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

et al. 2022

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“…The reported size and surface markers of human articular chondrocyte-derived EVs are similar to that of other cell-derived EVs. Although some reports highlighted that heterotrimeric G protein, HSP70 and 90, and members of the tetraspanin family such as CD9, CD63 and CD81 were not detected in the proteome of articular cartilage-derived EVs 52 , 53 , emerging research confirmed that CD9, CD63, and TSG101 proteins were expressed on chondrocyte-derived EVs 54 - 57 . Meanwhile, the content of EVs varies along with different types of tissues.…”

Section: The Biological and Pathophysiological Characteristics Of Evsmentioning

confidence: 99%

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Yin¹,

Ni²,

Witherel³

et al. 2022

Theranostics

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Osteoarthritis (OA) is a prevalent chronic whole-joint disease characterized by low-grade systemic inflammation, degeneration of joint-related tissues such as articular cartilage, and alteration of bone structures that can eventually lead to disability. Emerging evidence has indicated that synovium or articular cartilage-secreted extracellular vesicles (EVs) contribute to OA pathogenesis and physiology, including transporting and enhancing the production of inflammatory mediators and cartilage degrading proteinases. Bioactive components of EVs are known to play a role in OA include microRNA, long non-coding RNA, and proteins. Thus, OA tissues-derived EVs can be used in combination with advanced nanomaterial-based biosensors for the diagnostic assessment of OA progression. Alternatively, mesenchymal stem cell- or platelet-rich plasma-derived EVs (MSC-EVs or PRP-EVs) have high therapeutic value for treating OA, such as suppressing the inflammatory immune microenvironment, which is often enriched by pro-inflammatory immune cells and cytokines that reduce chondrocytes apoptosis. Moreover, those EVs can be modified or incorporated into biomaterials for enhanced targeting and prolonged retention to treat OA effectively. In this review, we explore recently reported OA-related pathological biomarkers from OA joint tissue-derived EVs and discuss the possibility of current biosensors for detecting EVs and EV-related OA biomarkers. We summarize the applications of MSC-EVs and PRP-EVs and discuss their limitations for cartilage regeneration and alleviating OA symptoms. Additionally, we identify advanced therapeutic strategies, including engineered EVs and applying biomaterials to increase the efficacy of EV-based OA therapies. Finally, we provide our perspective on the future of EV-related diagnosis and therapeutic potential for OA treatment.

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“…The thermocycling conditions were set at 95 C for 600 s, 45 cycles of 95 C for 10 s, and followed by 60 C for 1 min, as per methods described previously. 36 The expression level of the key genes was normalized to that of glyceraldehyde phosphate dehydrogenase (GAPDH) and was analyzed utilizing the comparative method 2 ÀDDCt . The PCR primers used in this study are listed in Table 2.…”

Section: Quantitative Real-time Pcr Assaymentioning

confidence: 99%

Analysis and identification of m6A RNA methylation regulators in metastatic osteosarcoma

Huang

Cui

Xiong

et al. 2022

Molecular Therapy - Nucleic Acids

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Osteosarcoma (OS) is characterized by rapid growth and early metastasis. However, its mechanism remains unclear. N 6 -methyladenosine (m 6 A) modification and its regulatory factors play essential roles in most cancers, including OS. In this study, we screened out 21 m 6 A modifiers using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, followed by the identification of the critical m 6 A methylation modifiers. The results revealed that the expression levels of three m 6 A methylation regulators, namely RBM15, METTL3, and LRPPRC, were associated with the low survival rate of patients with OS. We further studied the independent prognostic factors by performing univariate and multivariate Cox analyses and found that metastasis was an independent prognostic factor for patients with OS. Furthermore, we found for the first time that RBM15 was specific for metastatic OS rather than non-metastatic OS. Moreover, the significant overexpression of RBM15 was validated in metastatic OS cell lines and in actual human clinical specimens. We also revealed that RBM15 promoted the invasion, migration, and metastasis of OS cells through loss-functional and gainfunctional experiments and an animal metastatic model. In conclusion, RBM15 has a high correlation with OS metastasis formation and the decreased survival rate of patients with OS, and this may serve as a useful biomarker for predicting metastasis and prognosis of patients with OS.

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Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

Cited by 7 publications

References 31 publications

Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Analysis and identification of m6A RNA methylation regulators in metastatic osteosarcoma

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