bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–10–13
eight papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exosomal non-coding RNAs: Emerging insights into therapeutic potential and mechanisms in bone healing.
  2. Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds.
  3. Therapeutic combinations of exosomes alongside cancer stem cells (CSCs) and of CSC-derived exosomes (CSCEXs) in cancer therapy.
  4. The role of extracellular vesicles in cancer.
  5. Isolation and Characterization of Exosomes Derived from Mouse Spleen Tissues.
  6. Exosomes and Macrophages: Bidirectional Mutual Regulation in the Treatment of Diabetic Complications.
  7. Emerging understandings of the role of exosomes in atherosclerosis.
  8. Neuronal exosomes transport an miRISC cargo to preserve stem cell integrity during energy stress.
  1. J Tissue Eng. 2024 Jan-Dec;15:15 20417314241286606
    Exosomal non-coding RNAs: Emerging insights into therapeutic potential and mechanisms in bone healing.
    Huixin Shi, Yang Yang, Hao Xing, Jialin Jia, Wei Xiong, Shu Guo, Shude Yang.
      Exosomes are nano-sized extracellular vesicles (EVs) released by diverse types of cells, which affect the functions of targeted cells by transporting bioactive substances. As the main component of exosomes, non-coding RNA (ncRNA) is demonstrated to impact multiple pathways participating in bone healing. Herein, this review first introduces the biogenesis and secretion of exosomes, and elucidates the role of the main cargo in exosomes, ncRNAs, in mediating intercellular communication. Subsequently, the potential molecular mechanism of exosomes accelerating bone healing is elucidated from the following four aspects: macrophage polarization, vascularization, osteogenesis and osteoclastogenesis. Then, we systematically introduce construction strategies based on modified exosomes in bone regeneration field. Finally, the clinical trials of exosomes for bone healing and the challenges of exosome-based therapies in the biomedical field are briefly introduced, providing solid theoretical frameworks and optimization methods for the clinical application of exosomes in orthopedics.
    Keywords:  Exosomal non-coding RNAs; biomaterials; bone healing; engineered modification; mechanism
    DOI:  https://doi.org/10.1177/20417314241286606
  2. Stem Cell Res Ther. 2024 Oct 09. 15(1): 355
    Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds.
    Tasaduq Manzoor, Nida Farooq, Arushi Sharma, Parvaiz A Shiekh, Amreena Hassan, Lateef Ahmad Dar, Junaid Nazir, Meena Godha, Faheem A Sheikh, Mudasir Bashir Gugjoo, Sahar Saleem, Syed Mudasir Ahmad.
      Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair.
    Keywords:  Angiogenesis; Burns; Exosomes; Extracellular vesicles; Inflammation; miRNA
    DOI:  https://doi.org/10.1186/s13287-024-03970-3
  3. Cancer Cell Int. 2024 Oct 05. 24(1): 334
    Therapeutic combinations of exosomes alongside cancer stem cells (CSCs) and of CSC-derived exosomes (CSCEXs) in cancer therapy.
    Arefeh Zabeti Touchaei, Seyedeh Elham Norollahi, Ali Najafizadeh, Kosar Babaei, Elahe Bakhshalipour, Sogand Vahidi, Ali Akbar Samadani.
      Exosomes which are membrane vesicles released by cells have gained significant interest in the field of cancer therapy as a novel means of intercellular communication. Their role in immune activation and their pathophysiological functions in cancer therapy have been recognized. Exosomes carry diverse bioactive components including proteins, mRNA, microRNAs, and bioactive lipids. These molecules have therapeutic potential in promoting tissue regeneration, supporting stem cell activity, preventing cell death, modulating immune responses, and promoting the growth of new blood vessels. However, the precise roles of exosomes derived from mesenchymal stem cells (MSCs) in the treatment of various cancers are still not fully understood. Consequently, cancer stem cells (CSCs) can self-renew and differentiate into various cell types. Understanding the mechanisms that sustain their persistence is crucial for developing effective therapies. Exosomes have recently gained interest as vehicles for intercellular communication between CSCs and non-CSCs, influencing cancer progression and the microenvironment. Research is ongoing on the utilization of exosomes derived from cancer stem cells (CSC-Exosome) for cancer treatment. The composition of extracellular vesicles is influenced by the specific type and condition of the cells from which they are secreted. Circulating exosomes contain stable RNA molecules such as mRNAs, microRNAs, and long non-coding RNAs (lncRNAs). In this review, we will explore the significance of exosomes and their diverse cellular combinations in the context of cancer therapy.
    Keywords:  Cancer stem cells; Cancer therapy; Cellular combinations; Exosomes
    DOI:  https://doi.org/10.1186/s12935-024-03514-y
  4. Curr Top Membr. 2024 ;pii: S1063-5823(24)00018-8. [Epub ahead of print]94 247-285
    The role of extracellular vesicles in cancer.
    Elizabeth Cristina Perez Hurtado, Juan Sebastian Henao Agudelo, Rodrigo Augusto Foganholi da Silva, Thiago Albuquerque Viração, Célio Junior da Costa Fernandes.
      Extracellular vesicles (EVs), which include small EVs such as exosomes, play a critical role in intercellular communication and are produced by both cancer and non-cancer cells. Several studies have shown that cancer cells exploit various strategies to regulate the biogenesis, composition, and functions of EVs primarily to promote cancer progression. Given that exosomes originate from major sorting hubs at the limiting membrane of endosomes, they are central to a signaling network that connects external stimuli with intrinsic tumor cell features. Exosomes contain diverse repertoires of molecular cargos, such as proteins, lipids, and nucleic acids, which determine their heterogeneity and functional properties in cancer progression. Therefore, targeting exosome biogenesis will enhance our understanding of tumorigenesis and also promote the discovery of novel approaches for cancer therapy. In this chapter we summarize the machinery of exosome biogenesis and the local, distant, and systemic effects of exosomes released by cancer cells. Furthermore, we explore how these exosomes regulate the anti-tumor immune response and epigenetic mechanisms to sustain cancer progression and their implications in cancer prevention and treatment.
    Keywords:  Cancer progression; Cancer therapy; Cell communication; Epigenetic modifiers; Exosome; Immune surveillance; MicroRNAs; Rabs proteins; Small extracellular vesicles; Tumor microenvironment
    DOI:  https://doi.org/10.1016/bs.ctm.2024.06.010
  5. J Vis Exp. 2024 Sep 20.
    Isolation and Characterization of Exosomes Derived from Mouse Spleen Tissues.
    Yue Luo, Keyu Liu, Dongling Ling, Ting Gu, Liangqing Zhang, Wenliang Chen.
      Exosomes (Exo) are lipid-bilayer structures secreted by various cells, including those of animals, plants, and prokaryotes. Previous studies have revealed that Exo derived from humoral or cell-supernatant are promising targets for novel diagnostic or prognostic biomarkers, underscoring their significant role in disease pathogenesis. Tissue-derived Exo (Ti-Exo) have attracted increasing attention due to its ability to accurately reflect tissue specificity and the microenvironment. Ti-Exo, present in interstitial space, play crucial roles in intercellular communication and cross-organ signaling. Despite their recognized value in elucidating disease mechanisms, isolating Ti-Exo remains challenging due to the complexity of tissue matrices and variability in extraction methods. In this study, we developed a practical protocol for isolating exosomes from mice spleen tissue, providing a reproducible technique for subsequent identification analysis and functional studies. We used Type I collagenase digestion combined with differential ultracentrifugation to isolate spleen-derived Exo. The characteristics of isolated Exo were determined through electron microscopy, the nano-flow cytometer, and the western blot. The isolated spleen-derived Exo displayed the typical morphology of lipid bilayer vesicles, with particle sizes ranging from 30 nm to 150 nm. In addition, the expression profile of exosome markers confirmed the presence and purity of exosomes. Taken together, we successfully established a practical protocol for isolating spleen-derived Exo in mice.
    DOI:  https://doi.org/10.3791/67234
  6. Cell Mol Bioeng. 2024 Aug;17(4): 243-261
    Exosomes and Macrophages: Bidirectional Mutual Regulation in the Treatment of Diabetic Complications.
    Xue Li, Lianrong Yang, Shujun Xu, Yuan Tian, Xin Meng.
       Purpose: The bidirectional regulation of macrophages and exosomes provides a meaningful research direction for the treatment of complications arising from both type 1 and type 2 diabetes mellitus. However, there is currently no comprehensive evaluation of the bidirectional regulatory role of macrophages and exosomes in diabetic complications. In this review, we aim to provide the detailed process of the bidirectional regulation mechanism of macrophages and exosomes, and how macrophage-associated exosomes use this mechanism to make it better applied to clinical practice through biotechnology.
    Methods: Therefore, we summarized the bidirectional regulation mechanism of macrophages and exosomes and the application based on the bidirectional regulation mechanism from two aspects of inflammation and insulin resistance.
    Results: As key regulators of the immune system, macrophages are crucial in the progression of diabetic complications due to their significant impact on the regulation of cellular metabolism, inflammation, and insulin sensitivity. Furthermore, exosomes, as innovative mediators of intercellular communication, transport miRNAs, proteins, and various bioactive molecules, influencing the occurrence and progression of diabetic complications through the regulation of inflammation and insulin resistance. The bidirectional regulation between macrophages and exosomes provides a promising pathway for the treatment of diabetic complications aimed at regulating the immune response and improving insulin sensitivity.
    Conclusions: Understanding the complexity of the interaction between macrophages and exosomes can advance the treatment of diabetic complications and drug development, and bringing more innovative and effective treatment strategies for diabetic complications.
    Keywords:  Bidirectional mutual regulation; Diabetic complications treatment; Exosome; Macrophage
    DOI:  https://doi.org/10.1007/s12195-024-00816-z
  7. J Cell Physiol. 2024 Oct 06. e31454
    Emerging understandings of the role of exosomes in atherosclerosis.
    Zena Wehbe, Maya Wehbe, Ali Al Khatib, Ali H Dakroub, Gianfranco Pintus, Firas Kobeissy, Ali H Eid.
      Atherosclerosis remains a major contributor to cardiovascular disease, the leading cause of global morbidity and mortality. Despite the elucidation of several molecular, biochemical, and cellular aspects that contribute to the etio-pathogenesis of atherosclerosis, much remains to be understood about the onset and progression of this disease. Emerging evidence supports a role for exosomes in the cellular basis of atherosclerosis. Indeed, exosomes of activated monocytes seem to accentuate a positive feedback loop that promotes recruitment of pro-inflammatory leukocytes. Moreover, in addition to their role in promoting proliferation and invasion of vascular smooth muscle cells, exosomes can also induce neovascularization within lesions and increase endothelial permeability, two important features of fibrous plaques. Depending on their sources and cargo, exosomes can also induce clot formation and contribute to other hallmarks of atherosclerosis. Taken together, it is becoming increasingly evident that a better understanding of exosome biology is integral to elucidating the pathogenesis of atherosclerosis, and may thus provide insight into a potentially new therapeutic target for this disease.
    Keywords:  atherogenesis; cardiovascular disease; drug discovery; extracellular vesicles; phenotypic switch; vascular smooth muscle cells
    DOI:  https://doi.org/10.1002/jcp.31454
  8. Cell Rep. 2024 Oct 10. pii: S2211-1247(24)01202-6. [Epub ahead of print]43(10): 114851
    Neuronal exosomes transport an miRISC cargo to preserve stem cell integrity during energy stress.
    Christopher Wong, Elena M Jurczak, Richard Roy.
      During periods of nutrient scarcity, many animals undergo germline quiescence to preserve reproductive capacity, and neurons are often necessary for this adaptation. We show here that starvation causes the release of neuronal microRNA (miRNA)/Argonaute-loaded exosomes following AMP kinase-regulated trafficking changes within serotonergic neurons. This neuron-to-germline communication is independent of classical neurotransmission but instead relies on endosome-derived vesicles that carry a pro-quiescent small RNA cargo to modify germline gene expression. Using an miRNA activity sensor, we show that neuronally expressed miRNAs can extinguish the expression of germline mRNA targets in an exosome-dependent manner. Our findings demonstrate how an adaptive neuronal response can change gene expression at a distance by redirecting intracellular trafficking to release neuronal exosomes with specific miRNA cargoes capable of tracking to their appropriate destinations.
    Keywords:  Argonautes; C. elegans; CP: Developmental biology; CP: Stem cell research; dauer stage; developmental biology; energetic stress; exosomes; miRNA sensor; miRNAs; serotonergic neurons
    DOI:  https://doi.org/10.1016/j.celrep.2024.114851
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