bims-engexo Biomed News
on Engineered exosomes
Issue of 2024‒11‒03
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Engineered exosomes in service of tumor immunotherapy: From optimizing tumor-derived exosomes to delivering CRISPR/Cas9 system.
  2. A complete sojourn on exosomes: Potential diagnostic and therapeutic agents.
  3. Lipid Nanoparticle-Mediated Oip5-as1 Delivery Preserves Mitochondrial Function in Myocardial Ischemia/Reperfusion Injury by Inhibiting the p53 Pathway.
  4. Exosome-Laden Hydrogels as Promising Carriers for Oral and Bone Tissue Engineering: Insight into Cell-Free Drug Delivery.
  5. Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation.
  6. Plasma exosomes may mediate the development of lupus nephritis in patients with systemic lupus erythematosus.
  7. Delivering urokinase-type plasminogen activator using mulberry leaf exosomes enables thrombolysis and remodeling of venous microenvironments.
  1. Int J Cancer. 2024 Oct 30.
    Engineered exosomes in service of tumor immunotherapy: From optimizing tumor-derived exosomes to delivering CRISPR/Cas9 system.
    Mingyang Jiang, Ke Zhang, Jinfeng Meng, Linhua Xu, Ying Liu, Ruqiong Wei.
      Exosomes can be modified and designed for various therapeutic goals because of their unique physical and chemical characteristics. Researchers have identified tumor-derived exosomes (TEXs) as significant players in cancer by influencing tumor growth, immune response evasion, angiogeneis, and drug resistance. TEXs promote the production of specific proteins important for cancer progression. Due to their easy accessibility, TEXs are being modified through genetic, drug delivery, membrane, immune system, and chemical alterations to be repurposed as vehicles for delivering drugs to improve cancer treatment outcomes. In the complex in vivo environment, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) system encounters challenges from degradation, neutralization, and immune responses, emphasizing the need for strategic distribution strategies for effective genome editing. Engineered exosomes present a promising avenue for delivering CRISPR/Cas9 in vivo. In this review, we will explore different techniques for enhancing TEXs using various engineering strategies. Additionally, we will discuss how these exosomes can be incorporated into advanced genetic engineering systems like CRISPR/Cas9 for possible therapeutic uses.
    Keywords:  CRISPR/Cas9 system; engineered exosomes; exosomes; tumor immunotheraphy
    DOI:  https://doi.org/10.1002/ijc.35241
  2. Pathol Res Pract. 2024 Oct 28. pii: S0344-0338(24)00585-5. [Epub ahead of print]264 155674
    A complete sojourn on exosomes: Potential diagnostic and therapeutic agents.
    Sonakshi Garg, Gurisha Garg, Preeti Patel, Manish Kumar, Shubham Thakur, Nitin Sharma, Balak Das Kurmi.
      Exosomes are vesicles produced by the human body for carrying certain information from one cell to another. The carriers are nanosized vesicles carrying a wide variety of cargo like RNA, DNA, and proteins. Exosomes are also being used in the early diagnosis of various diseases and disorders. Current research focuses on exosomes tailoring for achieving therapeutic potential in various diseases and disorders. Besides this, their biocompatibility, stability, adjustable efficacy, and targeting properties make them attractive vehicles for formulation developers. Various preclinical studies suggested that the exosome culture cells are also modified with certain genes to achieve the desirable properties of resultant exosomes. The human body also produces some other vesicles like Ectosomes and Exomeres produced along with exosomes. Additionally, vesicles like Migrasomes are produced by migrating cells and apoptotic bodies, and Oncosomes are produced by cancer cells which can also be useful for the diagnosis of various diseases and disorders. For the separation of desired exosomes from other vesicles some latest techniques that can be useful viz differential centrifugation, density gradient centrifugation, and immunoaffinity purification have been discussed. Briefly, this review summarized various techniques of isolation of purified exosomes along with an overview of the application of exosomes in various neurodegenerative disorders and cancer along with various latest aspects of exosomes in disease progression and management which might be beneficial for the researchers.
    Keywords:  Cellular functions; Delivery Vehicle; Nanosized vesicles; RNA (siRNA); Therapeutics
    DOI:  https://doi.org/10.1016/j.prp.2024.155674
  3. ACS Appl Mater Interfaces. 2024 Nov 01.
    Lipid Nanoparticle-Mediated Oip5-as1 Delivery Preserves Mitochondrial Function in Myocardial Ischemia/Reperfusion Injury by Inhibiting the p53 Pathway.
    Xiaowei Niu, Jing Zhang, Jingjing Zhang, Lu Bai, Shuwen Hu, Zheng Zhang, Ming Bai.
      Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies in clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. Oip5-as1 may have potential as a therapeutic target for MI/R injury as its upregulated expression has been associated with reduced infarct size and improved cardiac function in animal models, although how to effectively and safely overexpress Oip5-as1 in vivo remains unclear. Lipid nanoparticles (LNPs) are a versatile technology for targeted drug delivery in numerous therapeutic applications. Herein, we aimed to assess the therapeutic efficacy and safety of LNPs coloaded with Oip5-as1 and a cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) in a murine model of MI/R injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. The structural components of LNP@Oip5-as1@CMP were physicochemically analyzed. A hypoxia/reoxygenation (H/R) model in HL-1 cells and coronary artery ligation in mice were used to simulate MI/R injury. Our results demonstrated that LNPs designed for cardiomyocyte targeting and efficient Oip5-as1 delivery were successfully synthesized. In HL-1 cells, LNP@Oip5-as1@CMP treatment significantly reduced mitochondrial apoptosis caused by H/R injury. In the murine MI/R model, the intravenous administration of LNP@Oip5-as1@CMP significantly decreased myocardial infarct size and improved cardiac function. Mechanistic investigations revealed that Oip5-as1 delivery inhibited the p53 signaling pathway. However, the cardioprotective effects of Oip5-as1 were abrogated by administrating Nutlin-3a, a p53 activator. Furthermore, no signs of major organ damage were detected after LNP@Oip5-as1@CMP injection. Our study reveals the therapeutic potential of LNPs for targeted Oip5-as1 delivery in mitigating MI/R injury. These findings pave the way for advanced targeted treatments in cardiovascular diseases, emphasizing the promise of lncRNA-based therapies.
    Keywords:  Oip5-as1; lipid nanoparticles; long noncoding RNAs; mitochondria; myocardial ischemia/reperfusion injury
    DOI:  https://doi.org/10.1021/acsami.4c10032
  4. Int J Mol Sci. 2024 Oct 15. pii: 11092. [Epub ahead of print]25(20):
    Exosome-Laden Hydrogels as Promising Carriers for Oral and Bone Tissue Engineering: Insight into Cell-Free Drug Delivery.
    Cassandra Villani, Prasathkumar Murugan, Anne George.
      Mineralization is a key biological process that is required for the development and repair of tissues such as teeth, bone and cartilage. Exosomes (Exo) are a subset of extracellular vesicles (~50-150 nm) that are secreted by cells and contain genetic material, proteins, lipids, nucleic acids, and other biological substances that have been extensively researched for bone and oral tissue regeneration. However, Exo-free biomaterials or exosome treatments exhibit poor bioavailability and lack controlled release mechanisms at the target site during tissue regeneration. By encapsulating the Exos into biomaterials like hydrogels, these disadvantages can be mitigated. Several tissue engineering approaches, such as those for wound healing processes in diabetes mellitus, treatment of osteoarthritis (OA) and cartilage degeneration, repair of intervertebral disc degeneration, and cardiovascular diseases, etc., have been exploited to deliver exosomes containing a variety of therapeutic and diagnostic cargos to target tissues. Despite the significant efficacy of Exo-laden hydrogels, their use in mineralized tissues, such as oral and bone tissue, is very sparse. This review aims to explore and summarize the literature related to the therapeutic potential of hydrogel-encapsulated exosomes for bone and oral tissue engineering and provides insight and practical procedures for the development of future clinical techniques.
    Keywords:  biomaterials; bone tissue engineering; exosomes; hydrogels; mineralized tissues; oral tissue engineering; regenerative medicine
    DOI:  https://doi.org/10.3390/ijms252011092
  5. Mol Med. 2024 Oct 26. 30(1): 186
    Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation.
    Yifei Nie, Wenqing Meng, Duanqin Liu, Ziqing Yang, Wenhao Wang, Huiping Ren, Kai Mao, Weipeng Lan, Chuanhua Li, Zhifeng Wang, Jing Lan.
      BACKGROUND: Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This study explores the therapeutic potential of exosomes sourced from SCAPs in the treatment of non-alcoholic steatohepatitis (NASH).METHODS: A NASH mouse model was established through the administration of a high-fat diet (HFD), and SCAPs were subsequently isolated for experimental purposes. A cell model of NASH was established in vitro by treating hepatocellular carcinoma cells with oleic acid (OA) and palmitic acid (PA). Exosomes were isolated via differential centrifugation. The mice were treated with exosomes injected into the tail vein, and the hepatocytes were incubated with exosomes in vitro. After the experiment, physiological and biochemical markers were analyzed to assess the effects of exosomes derived from SCAPs on the progression of NASH in both NASH mouse models and NASH cell models.
    RESULTS: After exosomes treatment, the weight gain and liver damage induced by HFD were significantly reduced. Additionally, hepatic fat accumulation was markedly alleviated. Mechanistically, exosomes treatment promoted the expression of genes involved in hepatic fatty acid oxidation and transport, while simultaneously suppressing genes associated with fatty acid synthesis. Furthermore, the levels of serum inflammatory cytokines and the mRNA expression of inflammatory markers in liver tissue were significantly decreased. In vitro cell experiments produced similar results.
    Keywords:  AMPK; Apical papilla stem cell-derived exosomes; NASH; PPARα
    DOI:  https://doi.org/10.1186/s10020-024-00945-1
  6. Lupus. 2024 Oct 31. 9612033241298047
    Plasma exosomes may mediate the development of lupus nephritis in patients with systemic lupus erythematosus.
    Jie Liu, Yuanju Liu, Yinde Xu, Jianjun Ye, Yun Zhu, Xiaolan Li.
      BACKGROUND: Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore the role of exosome-derived miRNA in the development of LN.METHODS: The publicly available data containing plasma exosomal miRNAs in SLE patients and healthy controls were researched, and differential expression and functional enrichment analysis of exosomal miRNA was conducted. Then, plasma exosomes from SLE patients were extracted, and the accuracy of differential expression and functional enrichment analysis was preliminarily verified. PKH26 dye was used to label exosomes to detect whether exosomes can enter HK2 cells. Evaluation of plasma exosomes impact on cell viability was done by utilizing CCK-8 assay. Flow cytometry was used to measure cell apoptosis.
    RESULTS: Plasma exosomes were successfully extracted and identified. Through differential expression analysis of the pulbilic data and subsequent qPCR validation, we observed that miR-20b-5p is overexpressed in plasma exosomes of SLE patients, whereas miR-181a-2-3p is downregulated. Then functional enrichment analysis revealed that these differential miRNAs primarily regulate processes such as apoptosis, autophagy, and inflammation. Then, flow cytometry analysis conducted after co-incubation of plasma exosomes and peripheral blood mononuclear cells confirmed that exosomes can indeed regulate apoptosis. And plasma exosomes can successfully enter HK2 cells without affecting cell activity. In addition, plasma exosomes promote HK2 cell apoptosis and autophagy. Overexpression of miR-181a-2-3p could inhibit HK2 cells apoptosis and upregulate the expression of bcl2, and beclin1. At the same time, a trend towards increased apoptosis rates was observed in HK2 overexpressed miR-20b-5p, although the difference did not reach statistical significance. And miR-20b-5p can enhance the expression of caspase3 and becin1 while suppressing the expression of bcl2 and LC3β.
    CONCLUSION: Our research indicates that the abundant presence of miR-20b-5p and the depletion of miR-181a-2-3p in plasma exosomes of SLE patients may mediate the promotion of apoptosis and autophagy in HK2 cells, thereby causing kidney damage and the development of LN.
    Keywords:  Lupus nephritis; apoptosis; autophagy; exosome; systemic lupus erythematosus
    DOI:  https://doi.org/10.1177/09612033241298047
  7. Int J Biol Macromol. 2024 Oct 23. pii: S0141-8130(24)07675-X. [Epub ahead of print] 136866
    Delivering urokinase-type plasminogen activator using mulberry leaf exosomes enables thrombolysis and remodeling of venous microenvironments.
    Pengpeng Guan, Caijie Yuan, Jiali Li, Kun Yu, Ruiqi Xie, Enling Hu, Weiwei Ding, Guangqian Lan, Fei Lu.
      In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of 'medicine food homology,' we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (-23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.
    Keywords:  Macrophage; Mulberry leaf exosomes; Reactive oxygen species; Thrombolysis; Urokinase-type plasminogen activator
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.136866
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