Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases

• Type of Material: Article
• Authors: Guoping Li, Massachusetts General Hospital; Tianji Chen, University of Illinois College of Medicine; James Dahlman, Emory University; Lola Eniola-Adefeso, University of Michigan, Ann Arbor; Ionita C Ghiran, Harvard Medical School; Peter Kurre, University of Pennsylvania Perelman School of Medicine; Wilbur Lam, Emory University; Jennifer K Lang, VA Western New York Healthcare System; Eduardo Marbán, Cedars-Sinai Medical Center; Pilar Martín, Centro de Investigación en Red en Enfermedades Cardiovasculares; Stefan Momma, Universitätsklinikum Frankfurt; Malcolm Moos, Food and Drug Administration; Deborah J Nelson, The University of Chicago; Robert L Raffai, San Francisco VA Health Care System; Xi Ren, Carnegie Mellon University; Joost PG Sluijter, University Medical Center Utrecht; Shannon L Stott, Massachusetts General Hospital Cancer Center; Gordana Vunjak-Novakovic, Columbia University; Nykia D Walker, University of Maryland, Baltimore County (UMBC); Zhenjia Wang, Washington State University Spokane; Kenneth W Witwer, Johns Hopkins School of Medicine; Philip C Yang, Stanford University School of Medicine; Martha S Lundberg, National Heart, Lung, and Blood Institute (NHLBI); Margaret J Ochocinska, National Heart, Lung, and Blood Institute (NHLBI); Renee Wong, National Heart, Lung, and Blood Institute (NHLBI); Guofei Zhou, National Heart, Lung, and Blood Institute (NHLBI); Stephen Y Chan, University of Pittsburgh School of Medicine; Saumya Das, Massachusetts General Hospital; Prithu Sundd, University of Pittsburgh School of Medicine
• Language: English
• Date: 2023-02-01
• Publisher: Wiley Periodicals, LLC
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jev2.12305
• Title of Journal or Parent Work: Journal of Extracellular Vesicles
• Volume: 12
• Issue: 2
• Start Page: e12305
• End Page: e12305
• Keywords: Cell Communication; therapeutics and diagnostics; Sleep; Nucleic Acids; Lung; extracellular vesicles (EVs); United States; Extracellular Vesicles; Heart, lung, blood and sleep (HLBS) diseases
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.