bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–12–08
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Editorial Commentary: M2 macrophage-derived exosomes promote tendon-to-bone healing by alleviating cellular senescence in aged rats.
  2. Circulating Extracellular Vesicles as Promising Biomarkers for Precession Diagnostics: A Perspective on Lung Cancer.
  3. GFP Farnesylation as a Suitable Strategy for Selectively Tagging Exosomes.
  4. Exosomal miR-20b-5p Induces EMT and Enhances Progression in Non-Small Cell Lung Cancer Via TGFBR2 Downregulation.
  5. Clinical applications of exosomes in cosmetic dermatology.
  6. Emerging role of exosomes during the pathogenesis of viral hepatitis, non-alcoholic steatohepatitis and alcoholic hepatitis.
  7. The Application of Salivary Exosomes in the Diagnosis of Oral Disease.
  8. Exosomes derived stem cells as a modern therapeutic approach for skin rejuvenation and hair regrowth.
  9. The role and clinical applications of exosomes in cancer drug resistance.
  10. Role of vascular endothelium and exosomes in cancer progression and therapy (Review).
  1. Arthroscopy. 2024 Nov 30. pii: S0749-8063(24)01008-9. [Epub ahead of print]
    Editorial Commentary: M2 macrophage-derived exosomes promote tendon-to-bone healing by alleviating cellular senescence in aged rats.
    Anne Gingery.
      Aging has long been associated with increased pathology in musculoskeletal tissues. Aging results in accumulation of senescent cells, stem cell exhaustion, sterile inflammation and immune cell dysfunction systemically and locally. Improving healing and regeneration during musculoskeletal aging is a significant area of clinical need. Recently the targeting of senescent cells has become an exciting area of research. Pathological accumulation of senescent cells in tissues is associated with tissue dysfunction. Immune system dysfunction has also been a proposed mechanism for the accumulation of senescent cells, where the immune system fails to clear senescent cells from tissue. Therapeutics that target senescent cells are an active area of research. Additionally stem cells in tissues decline with age. Stem cell exhaustion is one proposed mechanism for the declines in regeneration and healing that is found with aging. Declines in stem cells have been noted in patients with musculoskeletal injuries including rotator cuff tears. Shifts in immune cell populations has been shown to occur with aging and disease. The increase in sterile inflammation is associated with this shift in immune cell function. Polarized regenerative macrophages have been suggested to attenuate inflammation and promote healing. Exosomes from mesenchymal stem cells and immune cells, such as macrophages, are actively being pursued as important biologic therapies to improve regeneration and healing. Exosomes are small extracellular vesicles that are released from cells. Exosomes can carry DNA, RNA, lipids, and metabolites and appear to be important for intercellular communication. Assessing the efficacy of exosomes to promote healing and regeneration in musculoskeletal injuries in aged or diseased conditions is an active area of research. It is essential in this work to thoroughly define the cell sources of exosomes and determine their mechanistic response in tissues. Rigorous evidenced-based research is needed to determine the potential efficacy of exosomes to improve tissue healing for patients.
    DOI:  https://doi.org/10.1016/j.arthro.2024.11.078
  2. ACS Biomater Sci Eng. 2024 Dec 05.
    Circulating Extracellular Vesicles as Promising Biomarkers for Precession Diagnostics: A Perspective on Lung Cancer.
    Sunil Vasu, Vinith Johnson, Archana M, K Anki Reddy, Uday Kumar Sukumar.
      Extracellular vesicles (EVs) have emerged as promising biomarkers in liquid biopsy, owing to their ubiquitous presence in bodily fluids and their ability to carry disease-related cargo. Recognizing their significance in disease diagnosis and treatment, substantial efforts have been dedicated to developing efficient methods for EV isolation, detection, and analysis. EVs, heterogeneous membrane-encapsulated vesicles secreted by all cells, contain bioactive substances capable of modulating recipient cell biology upon internalization, including proteins, lipids, DNA, and various RNAs. Their prevalence across bodily fluids has positioned them as pivotal mediators in physiological and pathological processes, notably in cancer, where they hold potential as straightforward tumor biomarkers. This review offers a comprehensive examination of advanced nanotechnology-based techniques for detecting lung cancer through EV analysis. It begins by providing a brief overview of exosomes and their role in lung cancer progression. Furthermore, this review explores the evolving landscape of EV isolation and cargo analysis, highlighting the importance of characterizing specific biomolecular signatures within EVs for improved diagnostic accuracy in lung cancer patients. Innovative strategies for enhancing the sensitivity and specificity of EV isolation and detection, including the integration of microfluidic platforms and multiplexed biosensing technologies are summarized. The discussion then extends to key challenges associated with EV-based liquid biopsies, such as the standardization of isolation and detection protocols and the establishment of robust analytical platforms for clinical translation. This review highlights the transformative impact of EV-based liquid biopsy in lung cancer diagnosis, heralding a new era of personalized medicine and improved patient care.
    Keywords:  Exosomes; biosensors; early detection; liquid biopsy; lung cancer
    DOI:  https://doi.org/10.1021/acsbiomaterials.4c01323
  3. ACS Appl Bio Mater. 2024 Dec 05.
    GFP Farnesylation as a Suitable Strategy for Selectively Tagging Exosomes.
    Rebecca Piccarducci, Lorenzo Germelli, Alessandra Falleni, Lucrezia Luisotti, Benedetta Masciulli, Giovanni Signore, Chiara Migone, Angela Fabiano, Ranieri Bizzarri, Anna Maria Piras, Chiara Giacomelli, Laura Marchetti, Claudia Martini.
      Exosomes are small extracellular vesicles (EVs) constituting fully biological, cell-derived nanovesicles with great potential in cell-to-cell communication and drug delivery applications. The current gold standard for EV labeling and tracking is represented by fluorescent lipophilic dyes which, however, importantly lack selectivity, due to their unconditional affinity for lipids. Herein, an alternative EV fluorescent labeling approach is in-depth evaluated, by taking advantage of green fluorescent protein (GFP) farnesylation (GFP-f), a post-translational modification to directly anchor GFP to the EV membrane. The performance of GFP-f is analyzed, in terms of selectivity and efficiency, in several typical EV experimental setups such as delivery in recipient cells, surface engineering, and cargo loading. First, the capability of GFP and GFP-f to label exosomes was compared, showing significantly higher GFP protein levels and fluorescence intensity in GFP-f- than in GFP-labeled exosomes, highlighting the advantage of directly anchoring the GFP to the EV cell membrane. Then, the GFP-f tag was further compared to Vybrant DiD lipophilic dye labeling in exosome uptake studies, by capturing EV intracellular fluorescence in a time- and concentration-dependent manner. The internalization assay revealed a particular ability of GFP-f to monitor the uptake of tagged exosomes into recipient cells, with a significant peak of intensity reached 12 h after administration by GFP-f but not Vybrant-labeled EVs. Finally, the GFP-f labeling capability was challenged in the presence of a surface modification of exosomes and after transfection for siRNA loading. Results showed that both procedures can influence GFP-f performance compared to naïve GFP-f exosomes, although fluorescence is importantly maintained in both cases. Overall, these data provide direct insight into the advantages and limitations of GFP-f as a tagging protein for selectively and accurately tracking the exosome route from isolation to uptake in recipient cells, also in the context of EV bioengineering applications.
    Keywords:  GFP farnesylation (GFP-f); exosomes; extracellular vesicles; green fluorescent protein (GFP); labeling; loading; targeting; uptake
    DOI:  https://doi.org/10.1021/acsabm.4c01112
  4. J Biochem Mol Toxicol. 2024 Dec;38(12): e70080
    Exosomal miR-20b-5p Induces EMT and Enhances Progression in Non-Small Cell Lung Cancer Via TGFBR2 Downregulation.
    Hui Ma, Bo Jiang, Qiu Ren, Yajiao Sun, Mengyao Wang, Siyu Xia, Dong Wang, Wei Zhang.
      The mechanism by which specific miRNAs in NSCLC exosomes regulate NSCLC progression remains unclear. First, exosomes were isolated and identified. Exosomes were labeled with PKH26 for cell tracking studies. Subsequently, BEAS-2B cells and BEAS-2B cell exosomes were transfected with miR-20b-5p mimics or miR-20b-5p inhibitors, and cell proliferation was measured by EdU and CCK-8. cell migration and invasion were detected by wound healing tests and Transwell. The potential target of miR-20b-5p was predicted and verified by luciferase assay. Relative expression levels of miR-20b-5p and TGFBR2 were detected by qRT-PCR. Protein expression level was detected by Western blot. In addition, A549 cell exosomes were injected into mice through the tail vein and the pathological changes of lung tissue were detected by HE staining. Expression levels of E-cadherin and Vimentin in lung tissues were detected by immunohistochemistry. Our results also showed that high levels of miR-20b-5p in exosomes generated from NSCLC cells conceivably enter the cytoplasm of their own cells and by downregulating TGFBR2, accelerate NSCLC invasion, migration and EMT while promoting NSCLC cell proliferation. Exosome analysis using clinical plasma specimens revealed that miR-20b-5p expression was considerably improved in exosomes from NSCLC patients compared with those from healthy controls. In vitro and in vivo, exosomes with high levels of miR-20b-5p were linked to the progression of NSCLC. Our data suggest that exosomes with high levels of miR-20b-5p can increase development and metastasis of NSCLC cells by downregulating TGFBR2, which would serve as a predictive and diagnostic marker for NSCLC.
    Keywords:  TGFBR2; epithelial‐mesenchymal transition; exosomes; miR‐20b‐5p; non‐small cell lung cancer
    DOI:  https://doi.org/10.1002/jbt.70080
  5. Skin Health Dis. 2024 Dec;4(6): e348
    Clinical applications of exosomes in cosmetic dermatology.
    Ge Bai, Thu Minh Truong, Gaurav N Pathak, Lora Benoit, Babar Rao.
       Introduction: Exosomes are extracellular vesicles that transport bioactive substances during normal and abnormal cellular physiological processes. The unique properties of exosomes can be exploited for use as biomarkers and targeted drug delivery vehicles, and are, for this reason, gaining increasing attention in the field of dermatology. This review aims to synthesise the existing evidence supporting exosomes in regenerative and cosmetic dermatology.
    Method: A comprehensive PubMed search for the period of 2010-2023 was performed using the MeSH terms "exosome" and "skin." The initial search yielded 246 studies, which were then refined to 178 studies following title and abstract screening. Studies were confined to human or animal studies published in English that evaluated the use of exosomes in medical/cosmetic dermatology. A subsequent full-text review based on these criteria yielded 34 studies, which were then reviewed.
    Results: Exosomes can be derived from a variety of biological sources and show potential application in wound healing, scar prophylaxis, photodamage prevention, skin regeneration, improved grafting success, hair loss mitigation, and as biomarkers and drug carriers.
    Conclusion: Exosomes are gaining traction in regenerative and cosmetic dermatology. However, their widespread clinical application is hindered by cost, a complex isolation process, lack of uniform protocols, limited assessment of infective potential, and a paucity of clinical evidence. Further research in this area is needed, especially by way of clinical studies evaluating the efficacy of exosome-based treatments on human skin.
    DOI:  https://doi.org/10.1002/ski2.348
  6. Hum Cell. 2024 Dec 04. 38(1): 26
    Emerging role of exosomes during the pathogenesis of viral hepatitis, non-alcoholic steatohepatitis and alcoholic hepatitis.
    Congjian Shi, Shuang Hu, Shen Liu, Xiaodi Jia, Yubin Feng.
      Extracellular vesicles (EVs) refer to a diverse range of membranous vesicles that are secreted by various cell types, they can be categorized into two primary subgroups: exosomes and microvesicles. Specifically, exosomes constitute a nanosized subset of EVs characterized by their intact lipid bilayer and diameters ranging from 30 to 150 nm. These vesicles play a crucial role in intercellular communication by transporting a diverse array of biomolecules, which act as cargoes for this communication process. Exosomes have demonstrated significant implications in a wide range of biologic processes and pathologic conditions, including immunity, development, cancer, neurodegenerative diseases, and liver diseases. Liver diseases significantly contribute to the global burden of morbidity and mortality, yet their pathogenesis remains complex and effective therapies are relatively scarce. Emerging evidence suggests that exosomes play a modulatory role in the pathogenesis of liver diseases, including viral hepatitis, non-alcoholic steatohepatitis (NASH), and alcoholic hepatitis (AH). These findings bolster our confidence in the potential of exosomes as biomarkers and therapeutic tools for the diagnosis and treatment of liver diseases. In this comprehensive review, we offer a straightforward overview of exosomes and summarize the current understanding of their role in the pathogenesis of liver diseases. This provides a foundation for novel diagnostic and therapeutic approaches in the treatment of liver diseases.
    Keywords:  Alcoholic hepatitis; Exosomes; Liver diseases; Non-alcoholic steatohepatitis; Viral hepatitis
    DOI:  https://doi.org/10.1007/s13577-024-01158-8
  7. Chin J Dent Res. 2024 Dec 06. 27(4): 291-301
    The Application of Salivary Exosomes in the Diagnosis of Oral Disease.
    Ming Yang Yu, Xing Chi Liu, Zi Li Yu, Jun Jia.
      Oral diseases not only greatly impact patients' daily lives, but also pose a severe threat to their overall health. Due to the constant exposure of saliva to oral diseases, the former plays a vital role in their diagnosis and monitoring. Exosomes, nanosized bilayer lipid encapsulated nanovesicles, are widely present in saliva and can be released by any type of cell. Exosomes inherit features from their mother cells in both physiological and pathological conditions. The molecular characteristics and expression levels of exosomes depend on their cellular origin, and they can directly reflect the physiological state of the body and cells. This makes salivary exosomes a promising source for early detection and monitoring of oral diseases. As a result, researchers have been exploring the potential use of exosomes as biomarkers for diagnosing and predicting various oral diseases. This review provides an overview of the composition, separation and function of salivary exosomes. It also discusses their potential as diagnostic and prognostic markers for several oral diseases, including periodontitis, primary Sjögren's syndrome, oral mucosal diseases, hand-foot-mouth disease and oral squamous cell carcinoma. By studying salivary exosomes, researchers hope to improve the early detection and monitoring of oral diseases, leading to better outcomes for patients.
    Keywords:  diagnosis; liquid biopsy; oral disease; prediction; salivary exosomes
    DOI:  https://doi.org/10.3290/j.cjdr.b5860259
  8. Regen Ther. 2024 Jun;26 1124-1137
    Exosomes derived stem cells as a modern therapeutic approach for skin rejuvenation and hair regrowth.
    Fatemeh Norouzi, Sanaz Aghajani, Nasim Vosoughi, Shiva Sharif, Kazem Ghahremanzadeh, Zeinab Mokhtari, Javad Verdi.
       Background: The skin covers the surface of the body and acts as the first defense barrier against environmental damage. Exposure of the skin to environmental physical and chemical factors such as mechanical injuries, UV rays, air pollution, chemicals, etc. Leads to numerous damages to skin cells such as fibroblasts, keratinocytes, melanocytes, etc. The harmful effects of environmental factors on skin cells could lead to various skin diseases, chronic wounds, wrinkles, and skin aging. Hair is an essential part of the body, serving multiple functions such as regulating body temperature and protecting against external factors like dust (through eyelashes and eyebrows). It also reflects an individual's personality. Therefore, the need for new treatment methods for skin diseases and lesions and at the same time preserving the youth, freshness, and beauty of the skin has been highly noticed by experts. Exosomes are nanovesicles derived from cells that contain various biological compounds such as lipids, proteins, nucleic acids, and carbohydrates. They are secreted by a variety of mammalian cells and even different plants. Exosomes are of great interest as a new therapeutic approach due to their stability, ability to be transported throughout the body, paracrine and endocrine effects, as well as the ability to carry various compounds and drugs to target cells.
    Aim: In this review, we have discussed the characteristics of exosomes, their cellular sources, and their therapeutic effects on wrinkles, skin aging, and rejuvenation and hair regrowth.
    Keywords:  Exosomes; Hair regrowth; Skin aging; Skin rejuvenation; Wrinkles
    DOI:  https://doi.org/10.1016/j.reth.2024.10.001
  9. Cancer Drug Resist. 2024 ;7 43
    The role and clinical applications of exosomes in cancer drug resistance.
    Wenxuan Pan, Qun Miao, Wenqian Yin, Xiaobo Li, Wencai Ye, Dongmei Zhang, Lijuan Deng, Junqiu Zhang, Minfeng Chen.
      Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk and activating signaling pathways. Distinct from previous reviews, we focus intently on exosome-therapeutic resistance dynamics and summarize the new findings about the regulation of cancer treatment resistance by exosomes, shedding light on the complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies. Future research in exosome biology can potentially transform diagnostic paradigms and therapeutic interventions for cancer management. This review synthesizes recent insights into the exosome-driven regulation of cancer drug resistance, illuminates the sophisticated mechanisms by which these nanovesicles facilitate therapeutic refractoriness across various malignancies, and summarizes some strategies to overcome drug resistance.
    Keywords:  Exosome; drug resistance; implications for clinical treatment
    DOI:  https://doi.org/10.20517/cdr.2024.97
  10. Int J Oncol. 2025 Jan;pii: 6. [Epub ahead of print]66(1):
    Role of vascular endothelium and exosomes in cancer progression and therapy (Review).
    Yonghao Dai, Yutong Yao, Yuquan He, Xin Hu.
      Cancer poses a significant global health challenge and its progression is intricately connected to the interplay among various cell types and molecular pathways. In recent years, research has focused on the roles of vascular endothelial cells (VECs) and exosomes within the tumor microenvironment. Anomalies in tumor vascular integrity and function create a conducive milieu for cancer cell proliferation. Despite efforts in clinical anti‑angiogenic interventions, the anticipated outcomes remain elusive. VECs have the capability to transition into mesenchymal cells through endothelial‑to‑mesenchymal transition, thereby affecting cancer advancement. Exosomes are minute membrane‑bound vesicles generated by cells, serving as vital extracellular elements that facilitate cell‑to‑cell communication. They participate in modulating the tumor microenvironment, thereby influencing tumor progression, metastasis, drug resistance and angiogenesis. Additionally, exosomes serve as efficient carriers for drug delivery, as well as targeting and suppressing tumor cells. In summary, understanding the intricate and interconnected mechanisms of VECs and exosomes in cancer, encompassing tumor angiogenesis, microenvironment modulation and immune regulation, is crucial. A comprehensive exploration of these mechanisms may provide insight into cancer treatment and prevention and yield novel therapeutic targets.
    Keywords:  angiogenesis; cancer therapy; endothelial‑to‑mesenchymal transition; exosomes; vascular endothelium
    DOI:  https://doi.org/10.3892/ijo.2024.5712
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