Exosomes Digest (2/4 February 2025)
- Lisa
- Feb 10
- 5 min read
We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Exosomes and their distinct integrins transfer the characteristics of oxaliplatin- and 5-FU-resistant behaviors in colorectal cancer cells
Background
Exosomes are communication carriers and suitable biomarker candidates due to their cargoes with specific dynamic profiles. Integrins, as valuable prognostic markers in cancer, have importance in exosome-cell interaction. However, the role of exosome integrins in chemoresistant colorectal cancer remained unclear.
Methods
Oxaliplatin- and 5-FU-resistant cells (OXR and FUR) were established from human HCT-116 cells of colorectal cancer. Exosomes were collected from untreated and treated cells with oxaliplatin or 5-FU. Exosomes were isolated via ultracentrifugation and characterized using DLS and electron microscopy to evaluate size and morphology. Western blot analysis was employed to identify exosomal markers. The effects of exosomes on parental cells were examined using various methods, including MTT assay for proliferation, wound healing assay for migration, flow cytometry for cell cycle and apoptosis analysis, Matrigel-coated transwell inserts for invasion, and western blot for integrin expression evaluation.
Results
Exosome integrins determine resistance behaviors in cells. We observed that exosomes from OXR cells or OXR cells treated with oxaliplatin increased ITGβ3 expression and decreased ITGβ4 expression in parental cells, resulting in distinct resistance behaviors. Exosomes from FUR cells or FUR cells treated with 5-FU reduced ITGβ4 levels and elevated ITGαv levels in parental cells, leading to varying degrees of invasive resistance behaviors. These findings suggest that exosome integrins may affect these behaviors. High ITGβ3 exosomes induced oxaliplatin resistance behaviors in parental cells. Lowering ITGβ3 levels in these exosomes inhibited the resistance behaviors observed in these cells. FUR exosomes that overexpressed ITGαv or ITGβ4 resulted in invasive 5-FU resistance behaviors in parental cells. A reduction in these exosome integrin levels led to moderate invasive behaviors. The decrease of ITGβ4 in FUR cell exosomes inhibited resistant migration and proliferation in parental cells. A twofold reduction of ITGαv in FUR cell exosomes resulted in a threefold decrease in invasion and inhibited migration in parental cells compared to those treated with high ITGαv exosomes.
Conclusion
Our findings reveal that, despite discrepancies between cellular integrin patterns and cellular behaviors, the levels of exosomal ITGβ3, ITGαv, or ITGβ4 could serve as potential diagnostic and therapeutic markers for resistance to oxaliplatin and 5-FU in future cancer treatments.
A bibliometric analysis of exosomes in aging from 2007 to 2023
Background Aging is the primary factor contributing to the development of aging-related diseases. As research on exosomes continues to advance, its relationship with aging and aging-related diseases has become a hot topic This article analyzes the research hotspots of exosomes in aging and aging-related diseases, aiming to fill the gap in bibliometric research in this field and help researchers better understand the current status and future trends of both fundamental and clinical research in this field. Methods The articles were retrieved and exported from WoSCC on December 18, 2023. The visual analysis of countries and regions, institutions, authors, references, and keywords in exosomes of aging was conducted using VOSviewer 1.6.18, CiteSpace 6.2.R7, and Bibliometrix. Results The bibliometric analysis included 1628 articles. China and the United States emerged as the top two leading countries in this field. A total of 2,321 research institutions from 78 countries and regions were primarily led by China and the United States. Both Kapogiannis D and Goetzl E were active authors in this field. Thery C, Valadi H, and Raposo G were the important promoters in this field. Thery C proposed the method of differential centrifugation and density gradient centrifugation to extract exosomes. Valadi H discovered cells could send RNA-messages to each other by loading them into exosome-vesicles. The journal with the highest number of articles was International Journal of Molecular Sciences, while PLoS One was the most frequently cited journal. The keyword analysis revealed that future research on exosomes in aging will possibly focus on “inflammation, cellular senescence, angiogenesis, insulin resistance, and Alzheimer's disease.” Conclusion We identified the research trends of exosomes in the field of aging through this bibliometric analysis. The present study provides valuable new perspectives on the history and current status of exosomes in the field of aging and aging-related diseases, and also offering guidance for future research directions.
Adapted Exosomes for Addressing Chemotherapy-induced Premature Ovarian Insufficiency
Background
Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI.
Methods
Adapted exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs) under a specific co-culture system and used for treating in vitro and in vivo models of chemotherapy-induced premature ovarian insufficiency.
Results
In vitro models revealed the significant impact of adapted exosomes, which promoted granulosa cell proliferation, decrease apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model indicated the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and adapted exosome-treated groups. Notably, the adapted exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. MiRNA profiling revealed distinctive cargo in the adapted exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with adapted exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway—a crucial mechanism in mitigating chemotherapy-induced POI.
Conclusions
This study introduces an exosome-based therapeutic approach, emphasizing the importance of exosome cargo composition in treating disorders. Further investigation into the identified miRNA profile in adapted exosomes is necessary to clarify the underlying mechanisms, potentially leading to the development of a new treatment for clinical premature ovarian insufficiency.
Unravelling the role of stem cell-derived exosomes in oral cancer treatment: A review
Introduction: Oral cancer is the sixteenth most prevalent cancer globally, with Asian countries accounting for two-thirds of cases. Despite advancements in surgery, chemotherapy, and radiotherapy, late diagnosis, the absence of specific biomarkers, and the high cost of treatment result in poor outcomes. Tumor recurrence remains a significant challenge, highlighting the need for innovative therapeutic strategies. One promising avenue is the study of exosomes, which carry biomolecules like proteins, lipids, DNA, RNA, and microRNA, playing a key role in intercellular communication and the tumor microenvironment. Stem-cell-derived exosomes could revolutionize cancer therapy by targeting tumors and modulating immune responses. MicroRNAs within these exosomes are crucial in cancer progression, metastasis, and aggressiveness, contributing to high recurrence rates in oral cancer.
Methods: This review followed PRISMA-ScR guidelines to explore the therapeutic potential of stem cell-derived exosomes in oral cancer. A literature search in PubMed and Web of Science used terms related to "exosomes," "stem cells," and "oral cancer," including studies in English published before March 1, 2024. Original research, clinical trials, in vitro, and in vivo studies were selected; reviews and conference abstracts were excluded. Two reviewers independently screened and reviewed studies. Data extraction included study characteristics such as exosome origin, cargo, target cells, animal species, sample size, pathways, and primary outcomes.
Results: This review included nine studies, all conducted in vitro, with six also encompassing in vivo experiments. Notably, four of these studies were conducted in China. Findings suggest that stem cell-derived exosomes are promising candidates for oral cancer therapy, playing key roles in reducing pro-inflammatory cytokines, inducing apoptosis, enhancing cytotoxicity, inhibiting angiogenesis, and reducing oral cancer cell proliferation. The studies examined various types of exosomes derived from different stem cell sources, including umbilical cord mesenchymal stem cells, cancer stem cells, and other relevant tumor-related cells.
Conclusions: This review unravels the therapeutic potential of stem cell-derived exosomes as promising tools for oral cancer therapy. Exosomes derived from UC-MSCs, SHED, MenSCs, and hBMSCs reduce inflammation, induce apoptosis, and modulate angiogenesis and metastasis. Offering advantages over conventional treatments, such as low immunogenicity and targeted delivery, further research and clinical trials are essential to validate their safety, efficacy, and mechanisms.
