bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–11–10
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur



  1. ACS Appl Bio Mater. 2024 Nov 04.
      Extracellular vesicles (EVs) are cellular communication molecules and are classified into three major subpopulations, such as microvesicles, apoptotic bodies, and exosomes. Among these, exosomes-based cancer research is a cutting-edge investigation approach to cancer understanding. During cancer progression , tumor-derived exosomes can reprogram the cellular system and promote cancer. Circulating exosomes in the body fluids such as blood, plasma, serum, saliva, CSF, sweat, and tears play a key role in identifying diagnostic and prognostic cancer biomarkers. Diverse therapeutic sources of exosomes including stem cells, plants, and immune cells, etc. exhibit significant cancer-healing properties. Although cancer-targeting immunotherapy is an effective strategy, it has limitations such as toxicity, and high costs. In comparison, immune cell-derived exosomes-based immunotherapy is a cell-free approach for cancer treatment and has advantages like less toxicity, biocompatibility, reduced immunogenicity, and efficient, target-specific cancer therapeutic development. This review highlights the therapeutic signature of immune cell-derived exosomes for cancer treatment.
    Keywords:  Cancer; Exosomes; Extracellular vesicles; Immunotherapy; Metastasis
    DOI:  https://doi.org/10.1021/acsabm.4c00660
  2. Front Immunol. 2024 ;15 1473030
      In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.
    Keywords:  biological functions; diagnostic biomarker; exosomes; immunosuppression; liver cancer
    DOI:  https://doi.org/10.3389/fimmu.2024.1473030
  3. Adv Pharm Bull. 2024 Oct;14(3): 574-590
      Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton's jelly (WJ), adipose tissue and dental pulp (DP). These cells are capable of differentiating into the osteoblasts, chondrocytes, and adipocytes. Due to the unique characteristics of MSCs such as paracrine effects, immunomodulation, tumor-tropism, and migration, they are considered promising candidates for cancer therapeutics. Currently, MSCs are an excellent living carrier for delivery of therapeutic genes and chemical agents to target tumor sites. Also, exosomes, the most important extracellular vesicle released from MSCs, act as a strong cell-free tool for cancer therapeutics. MSCs can prevent cancer progression by inhibiting several signaling pathways, such as wnt/β-catenin and PI3K/AKT/mTOR. However, there are several challenges associated with the use of MSCs and their exosomes in the field of therapy that need to be considered. This review explores the significance of MSCs in cell-based therapy, focusing on their homing properties and immunomodulatory characteristics. It also examines the potential of using MSCs as carriers for delivery of anticancer agents and their role in modulating the signal transduction pathways of cancer cells.
    Keywords:  Cancer therapy; Cell therapy; Chemotherapeutic agents; Exosomes; Immunomodulation; Mesenchymal stem cells
    DOI:  https://doi.org/10.34172/apb.2024.052
  4. Heliyon. 2024 Oct 30. 10(20): e39251
      Diabetic foot ulcers (DFUs) represent a serious complication of diabetes with high incidence, requiring intensive treatment, prolonged hospitalization, and high costs. It poses a severe threat to the patient's life, resulting in substantial burdens on patient and healthcare system. However, the therapy of DFUs remains challenging. Therefore, exploring cell-free therapies for DFUs is both critical and urgent. Exosomes, as crucial mediators of intercellular communication, have been demonstrated potentially effective in anti-inflammation, angiogenesis, cell proliferation and migration, and collagen deposition. These functions have been proven beneficial in all stages of diabetic wound healing. This review aims to summarize the role and mechanisms of exosomes from diverse cellular sources in diabetic wound healing research. In addition, we elaborate on the challenges for clinical application, discuss the advantages of membrane vesicles as exosome mimics in wound healing, and present the therapeutic potential of exosomes and their mimetic vesicles for future clinical applications.
    Keywords:  Diabetic foot ulcers; Exosomes; Membrane vesicles; Regenerative medicine; Wound healing
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e39251
  5. Microbiol Res. 2024 Oct 31. pii: S0944-5013(24)00344-6. [Epub ahead of print]290 127943
      Exosomal microRNAs (miRNAs) in circulation were recognized as potential biomarkers for the diagnosis of multiple diseases. However, its potential as a diagnostic hallmark for tuberculosis (TB) has yet to be explored. Here, we comprehensively analyze miRNA profiles in exosomes derived from the plasma of active TB patients and healthy persons to evaluate its efficacy in TB diagnosis. Small-RNA transcriptomic profiling analysis identified a total of 14 differentially expressed miRNAs (DEmiRNAs), among which the diagnostic potential of exosomal miR-766-3p, miR-376c-3p, miR-1283, and miR-125a-5p was evident from their respective areas under the ROC curve, which were 0.8963, 0.8313, 0.8097, and 0.8050, respectively. The bioinformatics analysis and Luciferase reporter assays confirmed that the 3'-untranslated region of natural resistance-associated macrophage protein 1 (NRAMP1) mRNA was targeted by miR-766-3p. The exosomes could be internalized by the A549 cells in co-culturing experiments. Furthermore, both increased miR-766-3p and decreased NRAMP1 expression were observed in Mtb-infected A549 cells. MiR-766-3p overexpression reduced the NRAMP1 levels, but increased intracellular Mtb, suggesting that miR-766-3p may facilitate Mtb survival by targeting NRAMP1. Moreover, miR-766-3p-transfected cells exhibited increased apoptosis and reduced proliferation following Mtb infection. Taken together, circulating exosomal miR-766-3p, miR-1283, miR-125a-5p, and miR-376c-3p may serve as candidate hallmarks for TB diagnosis where the presence of miR-766-3p seems associated with the vulnerability to Mtb infection in humans and could be a new molecular target for therapeutic intervention of TB.
    Keywords:  Biomarker; Exosomes; Plasma; Tuberculosis (TB); miR-766–3p
    DOI:  https://doi.org/10.1016/j.micres.2024.127943
  6. Mol Neurobiol. 2024 Nov 06.
      The pathogenesis of autism spectrum disorder (ASD) is complex and is mainly influenced by genetic and environmental factors. Some research has indicated that environmental aspects may interplay with genetic aspects to enhance the risk, and microRNAs (miRNAs) are probably factors in explaining this link between heredity and the environment. MiRNAs are single-stranded noncoding RNAs that can regulate gene expression at the posttranscriptional level. Some research has indicated that miRNAs are closely linked to neurological diseases. Many aberrantly expressed miRNAs have been observed in autism, and these dysregulated miRNAs are expected to be potential biomarkers and provide new strategies for the treatment of this disease. This article reviews the research progress of miRNAs in autism, including their biosynthesis and function. It is found that some miRNAs show aberrant expression patterns in brain tissue and peripheral blood of autistic patients, which may serve as biomarkers of the disease. In addition, the article explores the novel role of exosomes as carriers of miRNAs with the ability to cross the blood-brain barrier and unique expression profiles, offering new possibilities for diagnostic and therapeutic interventions in ASD. The potential of miRNAs in exosomes as diagnostic markers for ASD is specifically highlighted, as well as the prospect of using engineered exosome-encapsulated miRNAs for targeted therapies.
    Keywords:  ASD; Biomarkers; Exosomes; MiRNAs; Therapeutic potential
    DOI:  https://doi.org/10.1007/s12035-024-04582-x
  7. Sci Rep. 2024 11 06. 14(1): 26860
      This study aimed to investigate the structural properties of tobacco polysaccharide (TP) and its mechanism of modulating hyperlipidemia in high-fat diet-induced mice. The structural properties of TP were characterized by FT-IR, 1HNMR, SEM, AFM and thermogravimetric analysis. And the regulatory mechanism of TP on lipid metabolism was investigated in hyperlipidemia mice. These results showed that TP had a high composition of reducing monosaccharide and the glycosidic bond type was α-glycosidic bond. The intervention by TP resulted in a significant reduction of body weight and improvement in lipid accumulation. And the modulation mechanism by which TP ameliorated the abnormalities of lipid metabolism was associated with the expression levels of lipid metabolism-related genes and serum exosomes miRNA-128-3p, as well as the modulation of structure and abundance of the gut microbiota in mice. In addition, TP treatment significantly increased the content of short-chain fatty acids (SCFAs) in mice feces. The results of molecular docking and dual-luciferase assay exhibited a good interaction between propionic acid and PPAR-α, and it was hypothesized that the interaction might further ameliorate the hyperlipidemia. Therefore, TP can regulate the expression levels of lipid metabolism-related genes through miRNAs from serum exosomes and SCFAs from gut microbiota.
    Keywords:  Gut microbiota; Modulation mechanism of hyperlipidemia; Serum exosomes; Tobacco polysaccharide (TP)
    DOI:  https://doi.org/10.1038/s41598-024-77514-3