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  1. Article ; Online: A roadmap towards manufacturing extracellular vesicles for cardiac repair.

    Louro, Ana F / Meliciano, Ana / Alves, Paula M / Costa, Marta H G / Serra, Margarida

    Trends in biotechnology

    2024  

    Abstract: For the past two decades researchers have linked extracellular vesicle (EV)-mediated mechanisms to various physiological and pathological processes in the heart, such as immune response regulation, fibrosis, angiogenesis, and the survival and growth of ... ...

    Abstract For the past two decades researchers have linked extracellular vesicle (EV)-mediated mechanisms to various physiological and pathological processes in the heart, such as immune response regulation, fibrosis, angiogenesis, and the survival and growth of cardiomyocytes. Although use of EVs has gathered momentum in the cardiac field, several obstacles in both upstream and downstream processes during EV manufacture need to be addressed before clinical success can be achieved. Low EV yields obtained in small-scale cultures deter clinical translation, as mass production is a prerequisite to meet therapeutic doses. Moreover, standardizing EV manufacture is critical given the inherent heterogeneity of EVs and the constraints of current isolation techniques. In this review, we discuss the critical steps for the large-scale manufacturing of high-potency EVs for cardiac therapies.
    Language English
    Publishing date 2024-04-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 47474-5
    ISSN 1879-3096 ; 0167-7799
    ISSN (online) 1879-3096
    ISSN 0167-7799
    DOI 10.1016/j.tibtech.2024.03.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Clinically Expired Platelet Concentrates as a Source of Extracellular Vesicles for Targeted Anti-Cancer Drug Delivery.

    Meliciano, Ana / Salvador, Daniela / Mendonça, Pedro / Louro, Ana Filipa / Serra, Margarida

    Pharmaceutics

    2023  Volume 15, Issue 3

    Abstract: The short shelf life of platelet concentrates (PC) of up to 5-7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. ... ...

    Abstract The short shelf life of platelet concentrates (PC) of up to 5-7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins. Nevertheless, synthetic drug delivery strategies have significant drawbacks that platelet-derived extracellular vesicles (pEV) can overcome. We investigated, for the first time, the use of pEV as a carrier of the anti-breast cancer drug paclitaxel, considering it as an appealing alternative to improve the therapeutic potential of expired PC. The pEV released during PC storage showed a typical EV size distribution profile (100-300 nm) with a cup-shaped morphology. Paclitaxel-loaded pEV showed significant anti-cancer effects in vitro, as demonstrated by their anti-migratory (>30%), anti-angiogenic (>30%), and anti-invasive (>70%) properties in distinct cells found in the breast tumor microenvironment. We provide evidence for a novel application for expired PC by suggesting that the field of tumor treatment research may be broadened by the use of natural carriers.
    Language English
    Publishing date 2023-03-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15030953
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  3. Article ; Online: Microfiber-reinforced hydrogels prolong the release of human induced pluripotent stem cell-derived extracellular vesicles to promote endothelial migration.

    Cedillo-Servin, Gerardo / Louro, Ana Filipa / Gamelas, Beatriz / Meliciano, Ana / Zijl, Anne / Alves, Paula M / Malda, Jos / Serra, Margarida / Castilho, Miguel

    Biomaterials advances

    2023  Volume 155, Page(s) 213692

    Abstract: Extracellular vesicle (EV)-based approaches for promoting angiogenesis have shown promising results. Yet, further development is needed in vehicles that prolong EV exposure to target organs. Here, we hypothesized that microfiber-reinforced gelatin ... ...

    Abstract Extracellular vesicle (EV)-based approaches for promoting angiogenesis have shown promising results. Yet, further development is needed in vehicles that prolong EV exposure to target organs. Here, we hypothesized that microfiber-reinforced gelatin methacryloyl (GelMA) hydrogels could serve as sustained delivery platforms for human induced pluripotent stem cell (hiPSC)-derived EV. EV with 50-200 nm size and typical morphology were isolated from hiPSC-conditioned culture media and tested negative for common co-isolated contaminants. hiPSC-EV were then incorporated into GelMA hydrogels with or without a melt electrowritten reinforcing mesh. EV release was found to increase with GelMA concentration, as 12 % (w/v) GelMA hydrogels provided higher release rate and total release over 14 days in vitro, compared to lower hydrogel concentrations. Release profile modelling identified diffusion as a predominant release mechanism based on a Peppas-Sahlin model. To study the effect of reinforcement-dependent hydrogel mechanics on EV release, stress relaxation was assessed. Reinforcement with highly porous microfiber meshes delayed EV release by prolonging hydrogel stress relaxation and reducing the swelling ratio, thus decreasing the initial burst and overall extent of release. After release from photocrosslinked reinforced hydrogels, EV remained internalizable by human umbilical vein endothelial cells (HUVEC) over 14 days, and increased migration was observed in the first 4 h. EV and RNA cargo stability was investigated at physiological temperature in vitro, showing a sharp decrease in total RNA levels, but a stable level of endothelial migration-associated small noncoding RNAs over 14 days. Our data show that hydrogel formulation and microfiber reinforcement are superimposable approaches to modulate EV release from hydrogels, thus depicting fiber-reinforced GelMA hydrogels as tunable hiPSC-EV vehicles for controlled release systems that promote endothelial cell migration.
    MeSH term(s) Humans ; Induced Pluripotent Stem Cells ; Hydrogels/pharmacology ; Human Umbilical Vein Endothelial Cells ; Extracellular Vesicles ; RNA
    Chemical Substances Hydrogels ; RNA (63231-63-0)
    Language English
    Publishing date 2023-11-07
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2772-9508
    ISSN (online) 2772-9508
    DOI 10.1016/j.bioadv.2023.213692
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  4. Article ; Online: International Society for Extracellular Vesicles Workshop. QuantitatEVs: multiscale analyses, from bulk to single extracellular vesicle.

    Basso, Manuela / Gori, Alessandro / Nardella, Caterina / Palviainen, Mari / Holcar, Marija / Sotiropoulos, Ioannis / Bobis-Wozowicz, Sylwia / D'Agostino, Vito G / Casarotto, Elena / Ciani, Yari / Suetsugu, Shiro / Gualerzi, Alice / Martin-Jaular, Lorena / Boselli, Daniela / Kashkanova, Anna / Parisse, Pietro / Lippens, Lien / Pagliuca, Martina / Blessing, Martin /
    Frigerio, Roberto / Fourniols, Thibaut / Meliciano, Ana / Fietta, Anna / Fioretti, Paolo Vincenzo / Soroczyńska, Karolina / Picciolini, Silvia / Salviano-Silva, Amanda / Bergese, Paolo / Zocco, Davide / Chiari, Marcella / Jenster, Guido / Waldron, Levi / Milosavljevic, Aleksandar / Nolan, John / Monopoli, Marco P / Witwer, Kenneth W / Bussolati, Benedetta / Di Vizio, Dolores / Falcon Perez, Juan / Lenassi, Metka / Cretich, Marina / Demichelis, Francesca

    Journal of extracellular biology

    2024  Volume 3, Issue 1

    Abstract: The 'QuantitatEVs: multiscale analyses, from bulk to single vesicle' workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single ... ...

    Abstract The 'QuantitatEVs: multiscale analyses, from bulk to single vesicle' workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV-associated molecular components and EV biophysical features, which are considered the core of EV-associated biomarker discovery and validation for their clinical translation. The in-person-only workshop was held in Trento, Italy, from January 31
    Language English
    Publishing date 2024-01-24
    Publishing country United States
    Document type Journal Article
    ISSN 2768-2811
    ISSN (online) 2768-2811
    DOI 10.1002/jex2.137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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