bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–07–14
eight papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. 3'-UTR Sequence of Exosomal NANOGP8 DNA as an Extracellular Vesicle-Localization Signal.
  2. The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis.
  3. Extracellular vesicles: Function, resilience, biomarker, bioengineering, and clinical implications.
  4. Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes.
  5. Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy.
  6. Mechanism of action of miR-15a-5p and miR-152-3p in paraquat-induced pulmonary fibrosis through Wnt/β-catenin signaling mediation.
  7. A systematic review of exosomes in remote ischemic conditioning.
  8. Urinary exosomes: Potential diagnostic markers and application in bladder cancer.
  1. Int J Mol Sci. 2024 Jul 02. pii: 7294. [Epub ahead of print]25(13):
    3'-UTR Sequence of Exosomal NANOGP8 DNA as an Extracellular Vesicle-Localization Signal.
    Manjusha Vaidya, Ayaka Kimura, Arjun Bajaj, Kiminobu Sugaya.
      Extracellular vesicles (EVs) are garnering attention as a safe and efficient biomolecule delivery system. EVs intrinsically play a crucial role in intercellular communication and pathophysiology by transporting functionally active DNA molecules. The internalized DNA pleiotropically affects the recipient cells. Considering these salient features, an intentional incorporation of specific DNA gene cassettes into EVs and their subsequent delivery to the target cells has potential applications in genetic engineering. Moreover, efficient ways to insert the DNA into EVs during their biogenesis is valuable. Our current research is a step in the development of this technology. As such, cancer cells are known to secrete exosomes containing increased amounts of double-stranded DNA than normal cells. The clonal analysis in our previously published data revealed that exosomes released from various cancer cells contained a significantly larger population of NANOGP8 DNA with a 22-base pair insertion in the 3'-untranslated region (UTR) compared to those secreted by normal cells. This finding led us to hypothesize that the 22-base pair insertion may act as a signal to facilitate the incorporation of NANOGP8 DNA into the exosomes. To test this hypothesis, we compared the EV localization of an Enhanced Green Fluorescent Protein (EGFP) gene fused with the NANOGP8 3'-UTR, with and without the 22-base pair insertion. The quantitative PCR analysis showed a significantly higher EGFP DNA accumulation in exosomes released from cells transfected with the gene cassette containing the 3'-UTR with the 22-base pair insertion. The discovery of a DNA localization signal in exosomal DNA's 3'-UTR could pave the way for the development of an EV-based DNA delivery system. This technology will open new possibilities in genetic engineering and innovative therapies using nucleic acid medicine.
    Keywords:  22-base pair insertion; NANOGP8 DNA; exosome-localization signal; extracellular vesicles; genetic engineering
    DOI:  https://doi.org/10.3390/ijms25137294
  2. Front Immunol. 2024 ;15 1417758
    The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis.
    Meijin Liu, Zhenzhen Wen, Tingting Zhang, Linghan Zhang, Xiaoyan Liu, Maoyuan Wang.
      Exosomes represent a type of extracellular vesicles derived from the endosomal pathway that transport diverse molecular cargoes such as proteins, lipids, and nucleic acids. These cargoes have emerged as crucial elements impacting disease diagnosis, treatment, and prognosis, and are integral to the process of exosome formation. This review delves into the essential molecular cargoes implicated in the phases of exosome production and release. Emphasis is placed on their significance as cancer biomarkers and potential therapeutic targets, accompanied by an exploration of the obstacles and feasible applications linked to these developments.
    Keywords:  biogenesis; diagnosis; exosomes; molecular cargo; treatment
    DOI:  https://doi.org/10.3389/fimmu.2024.1417758
  3. Tzu Chi Med J. 2024 Jul-Sep;36(3):36(3): 251-259
    Extracellular vesicles: Function, resilience, biomarker, bioengineering, and clinical implications.
    Der-Shan Sun, Hsin-Hou Chang.
      Extracellular vesicles (EVs) have emerged as key players in intercellular communication, disease pathology, and therapeutic innovation. Initially overlooked as cellular debris, EVs are now recognized as vital mediators of cell-to-cell communication, ferrying a cargo of proteins, nucleic acids, and lipids, providing cellular resilience in response to stresses. This review provides a comprehensive overview of EVs, focusing on their role as biomarkers in disease diagnosis, their functional significance in physiological and pathological processes, and the potential of bioengineering for therapeutic applications. EVs offer a promising avenue for noninvasive disease diagnosis and monitoring, reflecting the physiological state of originating cells. Their diagnostic potential spans a spectrum of diseases, including cancer, cardiovascular disorders, neurodegenerative diseases, and infectious diseases. Moreover, their presence in bodily fluids such as blood, urine, and cerebrospinal fluid enhances their diagnostic utility, presenting advantages over traditional methods. Beyond diagnostics, EVs mediate crucial roles in intercellular communication, facilitating the transfer of bioactive molecules between cells. This communication modulates various physiological processes such as tissue regeneration, immune modulation, and neuronal communication. Dysregulation of EV-mediated communication is implicated in diseases such as cancer, immune disorders, and neurodegenerative diseases, highlighting their therapeutic potential. Bioengineering techniques offer avenues for manipulating EVs for therapeutic applications, from isolation and purification to engineering cargo and targeted delivery systems. These approaches hold promise for developing novel therapeutics tailored to specific diseases, revolutionizing personalized medicine. However, challenges such as standardization, scalability, and regulatory approval need addressing for successful clinical translation. Overall, EVs represent a dynamic frontier in biomedical research with vast potential for diagnostics, therapeutics, and personalized medicine.
    Keywords:  Bioengineering for drug delivery; Cellular resilience; Clinical therapeutics; Disease biomarker; Extracellular vesicles
    DOI:  https://doi.org/10.4103/tcmj.tcmj_28_24
  4. Biochem Pharmacol. 2024 Jul 05. pii: S0006-2952(24)00396-4. [Epub ahead of print]226 116413
    Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes.
    Fan Yang, Donghua Cai, Ran Kong, Yuanjie Bi, Yu Zhang, Yu Lei, Yani Peng, Xia Li, Yang Xiao, Zhiguang Zhou, Haibo Yu.
      Chronic nonhealing diabetic wounds are a critical clinical challenge. Regulatory T cells (Tregs) are immunosuppressive modulators affecting wound healing progression by controlling the inflammatory response. The current study attempted to investigate whether the exosomes derived from cord blood (CB) Tregs can accelerate the healing process. Exosomes were isolated from CB-Treg cultures using ultracentrifugation and validated with different specific markers of exosomes. The purified CB-Treg-derived exosomes were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes. The migration-promoting effect of CB-Treg-derived exosomes on fibroblasts and endothelial cells was investigated. We used thermosensitive Pluronic F-127 hydrogel (PF-127) loaded with CB-Treg-derived exosomes in a diabetic wound healing mouse model. CB-Treg-derived exosomes with 30-120 nm diameters revealed exosome-specific markers, such as TSG101, Alix, and CD63. CB-Treg-derived exosomes were mainly bound to the monocytes when co-cultured with PBMCs, and promoted monocyte polarization to the anti-inflammatory phenotype (M2) in vitro. CB-Treg-derived exosomes enhanced the migration of endothelial cells and fibroblasts. Furthermore, CB-Treg-derived exosomes treatment accelerated wound healing by downregulating inflammatory factor levels and upregulating the M2 macrophage ratio in vivo. Our findings indicated that CB-Treg-derived exosomes could be a promising cell-free therapeutic strategy for diabetic wound healing, partly by targeting monocytes.
    Keywords:  Diabetic wound healing; Exosome; Monocyte; Regulatory T cell
    DOI:  https://doi.org/10.1016/j.bcp.2024.116413
  5. Angew Chem Int Ed Engl. 2024 Jul 08. e202404889
    Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy.
    Jicheng Wu, Hailin Lu, Ximing Xu, Lang Rao, Yun Ge.
      Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti-CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high-mannose glycans into the nanobodies against CD47 (HM-nCD47) and subsequently displayed HM-nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM-nCD47-CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose-binding lectin, all synergistically activating the macrophage-mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM-nCD47-CVs possessed significantly extended half-lives and increased accumulation at the tumor site, resulting in a remarkable macrophage-dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM-nCD47-CVs represent a new immunotherapeutic platform for cancer and other diseases.
    Keywords:  Cancer immunotherapy; Glycosylation; nanobody; vesicles
    DOI:  https://doi.org/10.1002/anie.202404889
  6. PeerJ. 2024 ;12 e17662
    Mechanism of action of miR-15a-5p and miR-152-3p in paraquat-induced pulmonary fibrosis through Wnt/β-catenin signaling mediation.
    Dong Liu, Yan Guan.
       Background: miRNAs are small, conserved, single-stranded non-coding RNA that are typically transported by exosomes for their functional roles. The therapeutic potential of exosomal miRNAs has been explored in various diseases including breast cancer, pancreatic cancer, cholangiocarcinoma, skin diseases, Alzheimer's disease, stroke, and glioma. Pathophysiological processes such as cellular inflammation, apoptosis, necrosis, immune dysfunction, and oxidative stress are closely associated with miRNAs. Internal and external factors such as tissue ischemia, hypoxia, pathogen infection, and endotoxin exposure can trigger these reactions and are linked to miRNAs. Paraquat-induced fibrosis is a protracted process that may not manifest immediately after injury but develops during bodily recovery, providing insights into potential miRNA intervention treatments.
    Rationale: These findings could potentially be applied for further pharmaceutical research and clinical therapy of paraquat-induced pulmonary fibrosis, and are likely to be of great interest to clinicians involved in lung fibrosis research.
    Methodology: Through a literature review, we identified an association between miR-15a-5p and miR-152-3p and their involvement in the Wnt signaling pathway. This allowed us to deduce the molecular mechanisms underlying regulatory interactions involved in paraquat-induced lung fibrosis.
    Results: miR-15a-5p and miR-152-3p play roles in body repair processes, and pulmonary fibrosis can be considered a form of reparative response by the body. Although the initial purpose of fibrotic repair is to restore normal body function, excessive tissue fibrosis, unlike scar formation following external skin trauma, can significantly and adversely affect the body. Modulating the Wnt/β-catenin signaling pathway is beneficial in alleviating tissue fibrosis in various diseases.
    Conclusions: In this study, we delineate the association between miR-15a-5p and miR-152-3p and the Wnt/β-catenin signaling pathway, presenting a novel concept for addressing paraquat-induced pulmonary fibrosis.
    Keywords:  Lung fibrosis; Mechanism; Paraquat; Wnt/β-catenin; miRNA
    DOI:  https://doi.org/10.7717/peerj.17662
  7. Biomed Pharmacother. 2024 Jul 10. pii: S0753-3322(24)01008-4. [Epub ahead of print]177 117124
    A systematic review of exosomes in remote ischemic conditioning.
    Mengqi Wang, Lina Jia, Jiahao Song, Xunming Ji, Ran Meng, Da Zhou.
       BACKGROUND: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC's protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication OBJECTIVE: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection.
    METHODS: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers.
    FINDINGS: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways.
    CONCLUSION: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research.
    Keywords:  Remote ischemic conditioning; exosome; microRNAs; organ protection
    DOI:  https://doi.org/10.1016/j.biopha.2024.117124
  8. Heliyon. 2024 Jun 30. 10(12): e32621
    Urinary exosomes: Potential diagnostic markers and application in bladder cancer.
    Ji Liu, Zhang Zhijin, Wentao Zhang, Maskey Niraj, Fuhan Yang, Guo Changcheng, Liliang Shen, Tianyuan Xu, Shenghua Liu, Zhang Junfeng, Shiyu Mao, Wei Li, Xudong Yao.
       Background: The exosome is a critical component of the intercellular communication., playing a vital role in regulating cell function. These small vesicles contain proteins, mRNAs, miRNAs, and lncRNAs, surrounded by lipid bilayer substances. Most cells in the human body can produce exosomes, released into various body fluids such as urine, blood, and cerebrospinal fluid. Bladder cancer is the most common tumor in the urinary system, with high recurrence and metastasis rates. Early diagnosis and treatment are crucial for improving patient outcomes.
    Methods: This study employed the PubMed search engine to retrieve publicly accessible data pertaining to urinary exosomes.
    Results: We summarize the origins and intricate biological characteristics of urinary exosomes, the introduction of research methodologies used in basic experiments to isolate and analyze these exosomes, the discussion of their applications and progress in the diagnosis and treatment of bladder cancer, and the exploration of the current limitations associated with using urinary exosomes as molecular biomarkers for diagnosing bladder cancer.
    Conclusion: Exosomes isolated from urine may be used as molecular biomarkers for early detection of bladder cancer.
    Keywords:  Biomarker; Bladder cancer diagnosis; Exosomes; Liquid biopsy; Urine
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e32621
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