Extracellular vesicles for tissue repair and regeneration: evidence, challenges and opportunities

Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages. During the last decade, EVs have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions. In this review paper, we report on the potential of EVs in tissue repair and regeneration. The regenerative properties that have been associated with EVs are explored, detailing the molecular cargo they carry that is capable of mediating such effects, the signaling cascades triggered in target cells and the functional outcome achieved. EV interactions and biodistribution in vivo that influence their regenerative effects are also described, particularly upon administration in combination with biomaterials. Finally, we review the progress that has been made for the successful implementation of EV regenerative therapies in a clinical setting

Upward trend in the use of psychostimulants by adults

Inzicht verkrijgen in de trends in het gebruik van psychostimulantia bij volwassenen. Opzet Retrospectief databaseonderzoek.Methode We selecteerden de gegevens van volwassenen (≥ 18 jaar) die minimaal 2 recepten binnen een jaar voor psychostimulantia hadden gekregen, uit IADB.nl, een Nederlandse database met gegevens over afgeleverde geneesmiddelen(59 apotheken, circa 600.000 patiënten). Wij berekenden zowel het aantal nieuwe als het totaal aantal gebruikersvan psychostimulantia per jaar over de jaren 2004-2014. Daarnaast onderzochten wij welk middel het meest werdvoorgeschreven en wie de behandeling had geïnitieerd.Resultaten Het aantal volwassenen dat psychostimulantia (methylfenidaat, dexamfetamine en amfetamine) kreeg voorgeschreven, steeg van 1,5 per 1000 volwassenen in 2004 naar 7,8 per 1000 volwassenen in 2014. De gebruikers warenveelal mannen (63,0%) en methylfenidaat was het meest voorgeschreven middel (85,7%). Het aantal nieuwegebruikers van deze middelen steeg van 0,5 naar 1,5 per 1000 volwassenen, waarbij er vooral een toename werdgezien onder jongvolwassenen (&lt; 30 jaar). Sinds 2012 lijkt het aantal nieuwe gebruikers zich te stabiliseren. Ongeveer 40% van de nieuwe behandelingen werd geïnitieerd door de huisarts.Conclusie De grote toename in het aantal volwassenen dat psychostimulantia krijgt voorgeschreven is grotendeels het gevolgvan een toename in het aantal nieuwe gebruikers, met name onder de jongvolwassenen. Aangezien psychostimulantia alleen zijn geregistreerd voor de behandeling van ADHD bij kinderen vanaf 6 jaar en adolescenten, en dusniet voor de behandeling van ADHD bij volwassenen, dienen kor te- en langetermijnef fec ten evenals bijwerkingenbij volwassenen beter onderzocht te worden.OBJECTIVE: To gain insight into the trends in the use of psychostimulants among adults.DESIGN: Retrospective database study.METHODS: We selected data on adults (≥ 18 years) who had had a minimum of 2 prescriptions for a psychostimulant drug within 1 year from IADB.nl, a Netherlands database of filled prescriptions (59 public pharmacies, approximately 600,000 patients). We calculated both the number of new users and the total number of users of psychostimulants per year in the period 2004-2014. We also assessed which agent was the most commonly prescribed psychostimulant drug and who had initiated treatment.RESULTS: The number of adults who were prescribed psychostimulants (methylphenidate, dexamphetamine and amphetamine) increased from 1.5 per 1000 adults in 2004 to 7.8 per 1000 adults in 2014. Users were mainly male (63.0%) and methylphenidate was the most frequently prescribed agent (85.7%). The number of new users of these agents increased from 0.5 to 1.5 per 1000 adults, and the greatest increase was observed among young adults (&lt; 30 years). The increase in new users seems to have stabilized since 2012. Around 40% of new treatments were initiated by the GP.CONCLUSION: The large increase in the number of adults who are prescribed psychostimulants seems mainly to be the result of an increase in the number of new users, especially among young adults. As psychostimulants are only approved for the treatment of ADHD in children from 6 years of age and in adolescents, short- and long-term effects and side effects of these drugs need to be better assessed in the adult population.</p

Stijgende lijn in het gebruik van psychostimulantia door volwassenen

OBJECTIVE: To gain insight into the trends in the use of psychostimulants among adults. DESIGN: Retrospective database study. METHODS: We selected data on adults (≥ 18 years) who had had a minimum of 2 prescriptions for a psychostimulant drug within 1 year from IADB.nl, a Netherlands database of filled prescriptions (59 public pharmacies, approximately 600,000 patients). We calculated both the number of new users and the total number of users of psychostimulants per year in the period 2004-2014. We also assessed which agent was the most commonly prescribed psychostimulant drug and who had initiated treatment. RESULTS: The number of adults who were prescribed psychostimulants (methylphenidate, dexamphetamine and amphetamine) increased from 1.5 per 1000 adults in 2004 to 7.8 per 1000 adults in 2014. Users were mainly male (63.0%) and methylphenidate was the most frequently prescribed agent (85.7%). The number of new users of these agents increased from 0.5 to 1.5 per 1000 adults, and the greatest increase was observed among young adults (< 30 years). The increase in new users seems to have stabilized since 2012. Around 40% of new treatments were initiated by the GP. CONCLUSION: The large increase in the number of adults who are prescribed psychostimulants seems mainly to be the result of an increase in the number of new users, especially among young adults. As psychostimulants are only approved for the treatment of ADHD in children from 6 years of age and in adolescents, short- and long-term effects and side effects of these drugs need to be better assessed in the adult population

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly