bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–06–16
fourteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. The science of exosomes: Understanding their formation, capture, and role in cellular communication.
  2. Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma.
  3. Bioinspired cellular membrane-derived vesicles for mRNA delivery.
  4. Tumor-associated macrophages derived exosomes; from pathogenesis to therapeutic opportunities.
  5. Exosomal microRNAs in hepatocellular carcinoma, expanding research field.
  6. Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus.
  7. Isolation and Characterization of Extracellular Vesicles Derived from Ex Vivo Culture of Visceral Adipose Tissue.
  8. Inter-laboratory multiplex bead-based surface protein profiling of MSC-derived EV preparations identifies MSC-EV surface marker signatures.
  9. ROS-responsive biomimetic nanosystem camouflaged by hybrid membranes of platelet-exosomes engineered with neuronal targeting peptide for TBI therapy.
  10. Clinical Translation of Inorganic Nanoparticles and Engineered Living Materials for Cancer Therapy.
  11. Role of aptamer technology in extracellular vesicle biology and therapeutic applications.
  12. Adipose-derived stem cell exosomes loaded with icariin attenuated M1 polarization of macrophages via inhibiting the TLR4/Myd88/NF-κB signaling pathway.
  13. Characterization of spinal cord tissue-derived extracellular vesicles in neuroinflammation.
  14. Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.
  1. Pathol Res Pract. 2024 Jul;pii: S0344-0338(24)00299-1. [Epub ahead of print]259 155388
    The science of exosomes: Understanding their formation, capture, and role in cellular communication.
    Kiavash Hushmandi, Seyed Hassan Saadat, Mehdi Raei, Amir Reza Aref, Russel J Reiter, Noushin Nabavi, Afshin Taheriazam, Mehrdad Hashemi.
      Extracellular vesicles (EVs) serve as a crucial method for transferring information among cells, which is vital in multicellular organisms. Among these vesicles, exosomes are notable for their small size, ranging from 20 to 150 nm, and their role in cell-to-cell communication. They carry lipids, proteins, and nucleic acids between cells. The creation of exosomes begins with the inward budding of the cell membrane, which then encapsulates various macromolecules as cargo. Once filled, exosomes are released into the extracellular space and taken up by target cells via endocytosis and similar processes. The composition of exosomal cargo varies, encompassing diverse macromolecules with specific functions. Because of their significant roles, exosomes have been isolated from various cell types, including cancer cells, endothelial cells, macrophages, and mesenchymal cells, with the aim of harnessing them for therapeutic applications. Exosomes influence cellular metabolism, and regulate lipid, glucose, and glutamine pathways. Their role in pathogenesis is determined by their cargo, which can manipulate processes such as apoptosis, proliferation, inflammation, migration, and other molecular pathways in recipient cells. Non-coding RNA transcripts, a common type of cargo, play a pivotal role in regulating disease progression. Exosomes are implicated in numerous biological and pathological processes, including inflammation, cancer, cardiovascular diseases, diabetes, wound healing, and ischemic-reperfusion injury. As a result, they hold significant potential in the treatment of both cancerous and non-cancerous conditions.
    Keywords:  Cancer; Endocytosis; Exosomes; Extracellular vesicles; Metabolism
    DOI:  https://doi.org/10.1016/j.prp.2024.155388
  2. Blood Adv. 2024 Jun 13. pii: bloodadvances.2023012464. [Epub ahead of print]
    Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma.
    Shushu Yuan, Qi Li, Chuan He, Mengli Bing, Xinyun Zhang, Hao Xu, Zhiming Wang, Meifang Zhao, Yuchen Zhang, Yali Chai, Bingzong Li, Wenzhuo Zhuang.
      Exosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared to conventional drug delivery systems. In this study, we developed a delivery platform utilizing exosomes derived from monocytes, specifically designed for targeted delivery of Bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B cell maturation antigen (anti-BCMA), as BCMA selectively expresses on myeloma cells. This modified anti-BCMA was then efficiently incorporated into the monocyte-derived exosomes. These adapted exosomes effectively encapsulated Bortezomib, leading to enhanced drug accessibility within MM cells and sustained intracellular accumulation over an extended period. Remarkably, our results demonstrated that anti-BCMA-Exo-Btz outperformed free Btz in vitro, exhibiting a more potent myeloma-suppressive effect. In orthotopic MM xenograft models, anti-BCMA-Exo-Btz exhibited a significant anti-tumor effect compared to free Btz. Furthermore, it demonstrated remarkable specificity in targeting Bortezomib to myeloma cells in vivo. Importantly, we observed no significant histological damage in mice treated with anti-BCMA-Exo-Btz and a slight effect on PBMCs. Additionally, our study highlighted the multifunctional potential of monocyte-exosomes, which induced cell apoptosis, mediated immune responses, and enhanced the osteogenic potential of mesenchymal stromal cells. In conclusion, our study suggests that exosomes modified with targeting ligands hold therapeutic promise for delivering Bortezomib to myelomas, offering substantial potential for clinical applications.
    DOI:  https://doi.org/10.1182/bloodadvances.2023012464
  3. Theranostics. 2024 ;14(8): 3246-3266
    Bioinspired cellular membrane-derived vesicles for mRNA delivery.
    Xiao Xu, Limei Xu, Jingzhi Wang, Caining Wen, Jiang Xia, Yuanmin Zhang, Yujie Liang.
      The rapid advancement of mRNA as vaccines and therapeutic agents in the biomedical field has sparked hope in the fight against untreatable diseases. Successful clinical application of mRNA therapeutics largely depends on the carriers. Recently, a new and exciting focus has emerged on natural cell-derived vesicles. These nanovesicles offer many functions, including enhanced drug delivery capabilities and immune evasion, thereby presenting a unique and promising platform for the effective and safe delivery of mRNA therapeutics. In this study, we summarize the characteristics and properties of biomimetic delivery systems for mRNA therapeutics. In particular, we discuss the unique features of cellular membrane-derived vesicles (CDVs) and the combination of synthetic nanovesicles with CDVs.
    Keywords:  cellular membrane-derived vesicles; exosomes; extracellular vesicle; mRNA delivery; mRNA vaccine
    DOI:  https://doi.org/10.7150/thno.93755
  4. Int Immunopharmacol. 2024 Jun 07. pii: S1567-5769(24)00926-3. [Epub ahead of print]136 112406
    Tumor-associated macrophages derived exosomes; from pathogenesis to therapeutic opportunities.
    Sara Hadad, Amirreza Khalaji, Amirreza Jabbaripour Sarmadian, Pooneh Jabbaripour Sarmadian, Elham Mohebi Janagard, Behzad Baradaran.
      Tumor-associated macrophages (TAMs) exert profound influences on cancer progression, orchestrating a dynamic interplay within the tumor microenvironment. Recent attention has focused on the role of TAM-derived exosomes, small extracellular vesicles containing bioactive molecules, in mediating this intricate communication. This review comprehensively synthesizes current knowledge, emphasizing the diverse functions of TAM-derived exosomes across various cancer types. The review delves into the impact of TAM-derived exosomes on fundamental cancer hallmarks, elucidating their involvement in promoting cancer cell proliferation, migration, invasion, and apoptosis evasion. By dissecting the molecular cargo encapsulated within these exosomes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and proteins, the review uncovers key regulatory mechanisms governing these effects. Noteworthy miRNAs, such as miR-155, miR-196a-5p, and miR-221-3p, are highlighted for their pivotal roles in mediating TAM-derived exosomal communication and influencing downstream targets. Moreover, the review explores the impact of TAM-derived exosomes on the immune microenvironment, particularly their ability to modulate immune cell function and foster immune evasion. The discussion encompasses the regulation of programmed cell death ligand 1 (PD-L1) expression and subsequent impairment of CD8 + T cell activity, unraveling the immunosuppressive effects of TAM-derived exosomes. With an eye toward clinical implications, the review underscores the potential of TAM-derived exosomes as diagnostic markers and therapeutic targets. Their involvement in cancer progression, metastasis, and therapy resistance positions TAM-derived exosomes as key players in reshaping treatment strategies. Finally, the review outlines future directions, proposing avenues for targeted therapies aimed at disrupting TAM-derived exosomal functions and redefining the tumor microenvironment.
    Keywords:  Cancer; Exosome; Extracellular vesicle; Therapeutic approach; Tumor-associated macrophages
    DOI:  https://doi.org/10.1016/j.intimp.2024.112406
  5. World J Gastroenterol. 2024 May 28. 30(20): 2618-2620
    Exosomal microRNAs in hepatocellular carcinoma, expanding research field.
    Bo-Hao Zheng, Xiao-Jian Ni, Hou-Bao Liu.
      In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. Small extracellular vesicles (exosomes) play important roles in the tumor microenvironment. In this review, the authors introduce the following points: (1) The composition and function of exosomal microRNAs (miRNAs) of different cell origins in hepatocellular carcinoma (HCC); (2) the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC; and (3) the potential applicability of exosomal miRNAs derived from mesen-chymal stem cells in the treatment of HCC. In addition, the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced. In this review, the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC, which provides a deeper understanding of exosomal miRNAs to the readers.
    Keywords:  Exosomes; Hepatocellular carcinoma; Liver cancer; MicroRNA; Tumor microenvironment
    DOI:  https://doi.org/10.3748/wjg.v30.i20.2618
  6. J Inflamm (Lond). 2024 Jun 12. 21(1): 20
    Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus.
    Shima Famil Samavati, Reza Yarani, Sara Kiani, Zohreh HoseinKhani, Masomeh Mehrabi, Steven Levitte, Rosita Primavera, Shashank Chetty, Avnesh S Thakor, Kamran Mansouri.
      Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.
    DOI:  https://doi.org/10.1186/s12950-024-00381-2
  7. Bio Protoc. 2024 Jun 05. 14(11): e5011
    Isolation and Characterization of Extracellular Vesicles Derived from Ex Vivo Culture of Visceral Adipose Tissue.
    Ankita Arora, Vinit Sharma, Rajesh Gupta, Anjali Aggarwal.
      Extracellular vesicles (EVs) are a heterogeneous group of nanoparticles possessing a lipid bilayer membrane that plays a significant role in intercellular communication by transferring their cargoes, consisting of peptides, proteins, fatty acids, DNA, and RNA, to receiver cells. Isolation of EVs is cumbersome and time-consuming due to their nano size and the co-isolation of small molecules along with EVs. This is why current protocols for the isolation of EVs are unable to provide high purity. So far, studies have focused on EVs derived from cell supernatants or body fluids but are associated with a number of limitations. Cell lines with a high passage number cannot be considered as representative of the original cell type, and EVs isolated from those can present distinct properties and characteristics. Additionally, cultured cells only have a single cell type and do not possess any cellular interactions with other types of cells, which normally exist in the tissue microenvironment. Therefore, studies involving the direct EVs isolation from whole tissues can provide a better understanding of intercellular communication in vivo. This underscores the critical need to standardize and optimize protocols for isolating and characterizing EVs from tissues. We have developed a differential centrifugation-based technique to isolate and characterize EVs from whole adipose tissue, which can be potentially applied to other types of tissues. This may help us to better understand the role of EVs in the tissue microenvironment in both diseased and normal conditions. Key features • Isolation of tissue-derived extracellular vesicles from ex vivo culture of visceral adipose tissue or any whole tissue. • Microscopic visualization of extracellular vesicles' morphology without dehydration steps, with minimum effect on their shape. • Flow cytometry approach to characterize the extracellular vesicles using specific protein markers, as an alternative to the time-consuming western blot.
    Keywords:  Extracellular vesicles; Flow cytometry; Tissue-derived EVs; Transmission electron microscopy; Visceral adipose tissue; Western blotting
    DOI:  https://doi.org/10.21769/BioProtoc.5011
  8. J Extracell Vesicles. 2024 Jun;13(6): e12463
    Inter-laboratory multiplex bead-based surface protein profiling of MSC-derived EV preparations identifies MSC-EV surface marker signatures.
    Vivian V T Nguyen, Joshua A Welsh, Tobias Tertel, Andre Choo, Simonides I van de Wakker, Kyra A Y Defourny, Bernd Giebel, Pieter Vader, Jayanthi Padmanabhan, Sai Kiang Lim, Esther N M Nolte-'t Hoen, Marianne C Verhaar, R Beklem Bostancioglu, Antje M Zickler, Jia Mei Hong, Jennifer C Jones, Samir El Andaloussi, Bas W M van Balkom, André Görgens.
      Mesenchymal stromal cells (MSCs) are promising regenerative therapeutics that primarily exert their effects through secreted extracellular vesicles (EVs). These EVs - being small and non-living - are easier to handle and possess advantages over cellular products. Consequently, the therapeutic potential of MSC-EVs is increasingly investigated. However, due to variations in MSC-EV manufacturing strategies, MSC-EV products should be considered as highly diverse. Moreover, the diverse array of EV characterisation technologies used for MSC-EV characterisation further complicates reliable interlaboratory comparisons of published data. Consequently, this study aimed to establish a common method that can easily be used by various MSC-EV researchers to characterise MSC-EV preparations to facilitate interlaboratory comparisons. To this end, we conducted a comprehensive inter-laboratory assessment using a novel multiplex bead-based EV flow cytometry assay panel. This assessment involved 11 different MSC-EV products from five laboratories with varying MSC sources, culture conditions, and EV preparation methods. Through this assay panel covering a range of mostly MSC-related markers, we identified a set of cell surface markers consistently positive (CD44, CD73 and CD105) or negative (CD11b, CD45 and CD197) on EVs of all explored MSC-EV preparations. Hierarchical clustering analysis revealed distinct surface marker profiles associated with specific preparation processes and laboratory conditions. We propose CD73, CD105 and CD44 as robust positive markers for minimally identifying MSC-derived EVs and CD11b, CD14, CD19, CD45 and CD79 as reliable negative markers. Additionally, we highlight the influence of culture medium components, particularly human platelet lysate, on EV surface marker profiles, underscoring the influence of culture conditions on resulting EV products. This standardisable approach for MSC-EV surface marker profiling offers a tool for routine characterisation of manufactured EV products in pre-clinical and clinical research, enhances the quality control of MSC-EV preparations, and hopefully paves the way for higher consistency and reproducibility in the emerging therapeutic MSC-EV field.
    Keywords:  MSC; MSC‐marker; culture conditions; exosomes; extracellular vesicles; inter‐laboratory assessment; mesenchymal stromal cells; quality control; regenerative medicine; standardisation; surface markers
    DOI:  https://doi.org/10.1002/jev2.12463
  9. J Control Release. 2024 Jun 06. pii: S0168-3659(24)00366-3. [Epub ahead of print]
    ROS-responsive biomimetic nanosystem camouflaged by hybrid membranes of platelet-exosomes engineered with neuronal targeting peptide for TBI therapy.
    Yi Li, Xin Xin, Xun Zhou, Jingzhou Liu, Hangbing Liu, Shuo Yuan, Hanhan Liu, Wenyan Hao, Jiejie Sun, Yuli Wang, Wei Gong, Meiyan Yang, Zhiping Li, Yang Han, Chunsheng Gao, Yang Yang.
      Recovery and survival following traumatic brain injury (TBI) depends on optimal amelioration of secondary injuries at lesion site. Delivering mitochondria-protecting drugs to neurons may revive damaged neurons at sites secondarily traumatized by TBI. Pioglitazone (PGZ) is a promising candidate for TBI treatment, limited by its low brain accumulation and poor targetability to neurons. Herein, we report a ROS-responsive nanosystem, camouflaged by hybrid membranes of platelets and engineered extracellular vesicles (EVs) (C3-EPm-|TKNPs|), that can be used for targeted delivery of PGZ for TBI therapy. Inspired by intrinsic ability of macrophages for inflammatory chemotaxis, engineered M2-like macrophage-derived EVs were constructed by fusing C3 peptide to EVs membrane integrator protein, Lamp2b, to confer them with ability to target neurons in inflamed lesions. Platelets provided hybridized EPm with capabilities to target hemorrhagic area caused by trauma via surface proteins. Consequently, C3-EPm-|PGZ-TKNPs| were orientedly delivered to neurons located in the traumatized hemisphere after intravenous administration, and triggered the release of PGZ from TKNPs via oxidative stress. The current work demonstrate that C3-EPm-|TKNPs| can effectively deliver PGZ to alleviate mitochondrial damage via mitoNEET for neuroprotection, further reversing behavioral deficits in TBI mice. Our findings provide proof-of-concept evidence of C3-EPm-|TKNPs|-derived nanodrugs as potential clinical approaches against neuroinflammation-related intracranial diseases.
    Keywords:  C3-expressing extracellular vesicles; Pioglitazone; Platelet membrane; ROS-responsive; Traumatic brain injury
    DOI:  https://doi.org/10.1016/j.jconrel.2024.06.018
  10. Chempluschem. 2024 Jun 11. e202400090
    Clinical Translation of Inorganic Nanoparticles and Engineered Living Materials for Cancer Therapy.
    Lucia Gandarias, Damien Faivre.
      A wide range of particle-based nano- to microsystems is currently under investigation for potential use in personalized nanomedicine. However, only a small fraction of these innovations is likely to make it to clinical use. In this concept article, we start by discussing the potential applications of inorganic nanoparticles in cancer treatment and diagnosis, and shed light on the challenges they must overcome to become clinically available. In the second part, we delve into engineered living materials, which have begun to revolutionize the way medical interventions could be performed. Finally, we share our insights and opinions to explain why, despite significant advancements in research on these technologies, their translation to clinical practice remains limited.
    Keywords:  Nanoparticles; drugs; imaging; targeting; theranostics
    DOI:  https://doi.org/10.1002/cplu.202400090
  11. Nanoscale. 2024 Jun 10.
    Role of aptamer technology in extracellular vesicle biology and therapeutic applications.
    Rocky Chowdhury, Sadegh Eslami, Cuong Viet Pham, Alin Rai, Jia Lin, Yingchu Hou, David W Greening, Wei Duan.
      Extracellular vesicles (EVs) are cell-derived nanosized membrane-bound vesicles that are important intercellular signalling regulators in local cell-to-cell and distant cell-to-tissue communication. Their inherent capacity to transverse cell membranes and transfer complex bioactive cargo reflective of their cell source, as well as their ability to be modified through various engineering and modification strategies, have attracted significant therapeutic interest. Molecular bioengineering strategies are providing a new frontier for EV-based therapy, including novel mRNA vaccines, antigen cross-presentation and immunotherapy, organ delivery and repair, and cancer immune surveillance and targeted therapeutics. The revolution of EVs, their diversity as biocarriers and their potential to contribute to intercellular communication, is well understood and appreciated but is ultimately dependent on the development of methods and techniques for their isolation, characterization and enhanced targeting. As single-stranded oligonucleotides, aptamers, also known as chemical antibodies, offer significant biological, chemical, economic, and therapeutic advantages in terms of their size, selectivity, versatility, and multifunctional programming. Their integration into the field of EVs has been contributing to the development of isolation, detection, and analysis pipelines associated with bioengineering strategies for nano-meets-molecular biology, thus translating their use for therapeutic and diagnostic utility.
    DOI:  https://doi.org/10.1039/d4nr00207e
  12. Int Immunopharmacol. 2024 Jun 12. pii: S1567-5769(24)00969-X. [Epub ahead of print]137 112448
    Adipose-derived stem cell exosomes loaded with icariin attenuated M1 polarization of macrophages via inhibiting the TLR4/Myd88/NF-κB signaling pathway.
    Qiqi Yan, Changheng Song, Haixia Liu, Yubo Li, Jiayi Ma, Yukun Zhao, Zhiqian Song, Yanjing Chen, Ruyuan Zhu, Zhiguo Zhang.
      Abnormal macrophage polarization is one of the common pathological bases of various inflammatory diseases. The current research focus involves targeting macrophages to remodel their phenotype as a treatment approach for inflammatory diseases. Notably, exosomes can be delivered to specific types of cells or tissues or inflammatory area to realize targeted drug delivery. Although icariin (ICA) exhibits regulatory potential in macrophage polarization, the practical application of ICA is impeded by its water insolubility, poor permeability, and low bioavailability. Exploiting the inherent advantages of exosomes as natural drug carriers, we introduce a novel drug delivery system-adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA. High-performance liquid chromatography analysis confirmed a loading rate of 92.7 ± 0.01 % for ADSCs-EXO-ICA, indicating the successful incorporation of ICA. As demonstrated by cell counting kit-8 assays, ADSCs-EXO exerted a significantly higher promotion effect on macrophage proliferation. The subsequent experimental results revealed the superior anti-inflammatory effect of ADSCs-EXO-ICA compared to individual treatments with EXO or ICA in the lipopolysaccharide + interferon-gamma-induced M1 inflammation model. Additionally, results from enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and western blot analyses revealed that ADSCs-EXO-ICA effectively inhibited macrophage polarization toward the M1-type and concurrently promoted polarization toward the M2-type. The underlying mechanism involved the modulation of macrophage polarization through inhibition of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-kappa B signaling pathway, thereby mitigating inflammation. These findings underscore the potential therapeutic value of ADSCs-EXO-ICA as a novel intervention for inflammatory diseases.
    Keywords:  Anti-inflammatory; Exosomes; Human adipose-derived stem cells; Icariin; Macrophage polarization
    DOI:  https://doi.org/10.1016/j.intimp.2024.112448
  13. J Neuroinflammation. 2024 Jun 08. 21(1): 154
    Characterization of spinal cord tissue-derived extracellular vesicles in neuroinflammation.
    Larissa Jank, Ajay Kesharwani, Taekyung Ryu, Deepika Joshi, Dimitrios C Ladakis, Matthew D Smith, Saumitra Singh, Tanina Arab, Kenneth W Witwer, Peter A Calabresi, Chan-Hyun Na, Pavan Bhargava.
      Extracellular vesicles (EVs) are released by all cells, can cross the blood-brain barrier, and have been shown to play an important role in cellular communication, substance shuttling, and immune modulation. In recent years EVs have shifted into focus in multiple sclerosis (MS) research as potential plasma biomarkers and therapeutic vehicles. Yet little is known about the disease-associated changes in EVs in the central nervous system (CNS). To address this gap, we characterized the physical and proteomic changes of mouse spinal cord-derived EVs before and at 16 and 25 days after the induction of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model of MS. Using various bioinformatic tools, we found changes in inflammatory, glial, and synaptic proteins and pathways, as well as a shift in the predicted contribution of immune and glial cell types over time. These results show that EVs provide snapshots of crucial disease processes such as CNS-compartmentalized inflammation, re/de-myelination, and synaptic pathology, and might also mediate these processes. Additionally, inflammatory plasma EV biomarkers previously identified in people with MS were also altered in EAE spinal cord EVs, suggesting commonalities of EV-related pathological processes during EAE and MS and overlap of EV proteomic changes between CNS and circulating EVs.
    Keywords:  EAE; Extracellular vesicles; Multiple sclerosis; Myelin; Neuroinflammation; Synaptic pathology; Tissue-derived extracellular vesicles
    DOI:  https://doi.org/10.1186/s12974-024-03147-y
  14. Invest Ophthalmol Vis Sci. 2024 Jun 03. 65(6): 16
    Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.
    Jinghua Liu, Juan Gao, Ping Lu, Yuchuan Wang, Shulei Xing, Yarong Yan, Ruifang Han, Peng Hao, Xuan Li.
       Purpose: Corneal injury (CI) resulting in corneal opacity remains a clinical challenge. Exosomes (Exos) derived from bone marrow mesenchymal stem cells (BMSCs) have been proven effective in repairing various tissue injuries and are also considered excellent drug carriers due to their biological properties. Recently, microRNA-29b (miR-29b) was found to play an important role in the autophagy regulation which correlates with cell inflammation and fibrosis. However, the effects of miR-29b and autophagy on CI remain unclear. To find better treatments for CI, we used Exos to carry miR-29b and investigated its effects in the treatment of CI.
    Methods: BMSCs were transfected with miR-29b-3p agomir/antagomir and negative controls (NCs) to obtain Exos-29b-ago, Exos-29b-anta, and Exos-NC. C57BL/6J mice that underwent CI surgeries were treated with Exos-29b-ago, Exos-29b-anta, Exos-NC, or PBS. The autophagy, inflammation, and fibrosis of the cornea were estimated by slit-lamp, hematoxylin and eosin (H&E) staining, immunofluorescence, RT‒qPCR, and Western blot. The effects of miR-29b-3p on autophagy and inflammation in immortalized human corneal epithelial cells (iHCECs) were also investigated.
    Results: Compared to PBS, Exos-29b-ago, Exos-29b-anta, and Exos-NC all could ameliorate corneal inflammation and fibrosis. However, Exos-29b-ago, which accumulated a large amount of miR-29b-3p, exerted excellent potency via autophagy activation by inhibiting the PI3K/AKT/mTOR pathway and further inhibited corneal inflammation via the mTOR/NF-κB/IL-1β pathway. After Exos-29b-ago treatment, the expressions of collagen type III, α-smooth muscle actin, fibronectin, and vimentin were significantly decreased than in other groups. In addition, overexpression of miR-29b-3p prevented iHCECs from autophagy impairment and inflammatory injury.
    Conclusions: Exos from BMSCs carrying miR-29b-3p can significantly improve the therapeutic effect on CI via activating autophagy and further inhibiting corneal inflammation and fibrosis.
    DOI:  https://doi.org/10.1167/iovs.65.6.16
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