Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases
Li, Guoping; Chen, Tianji; Dahlman, James; Eniola-Adefeso, Lola; Ghiran, Ionita C.; Kurre, Peter; Lam, Wilbur A.; Lang, Jennifer K.; Marbán, Eduardo; Martín, Pilar; Momma, Stefan; Moos, Malcolm; Nelson, Deborah J.; Raffai, Robert L.; Ren, Xi; Sluijter, Joost P.G.; Stott, Shannon L.; Vunjak-Novakovic, Gordana; Walker, Nykia D.; Wang, Zhenjia; Witwer, Kenneth W.; Yang, Phillip C.; Lundberg, Martha S.; Ochocinska, Margaret J.; Wong, Renee; Zhou, Guofei; Chan, Stephen Y.; Das, Saumta; Sundd, Prithu
(2023) Journal of Extracellular Vesicles, volume 12, issue 2
(Article)
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
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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.
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Keywords: extracellular vesicles (EVs), Heart, lung, blood and sleep (HLBS) diseases, therapeutics and diagnostics, Histology, Cell Biology
ISSN: 2001-3078
Publisher: John Wiley & Sons Inc.
Note: Funding Information: Prithu Sundd received funding as a part of sponsored research agreements with CSL Behring Inc., IHP Therapeutics and Novartis Pharmaceuticals Corporation. He is also the recipient of Bayer Hemophilia Award and has filed patent application targeting Gasdermin‐D to prevent lung injury in Sickle Cell Disease. Stephen Y. Chan has served as a consultant for Acceleron Pharma and United Therapeutics. He is a director, officer and shareholder in Synhale Therapeutics and has held research grants from Actelion, Bayer and Pfizer. Stephen Y. Chan has also filed patent applications regarding the targeting of metabolism in pulmonary hypertension. Kenneth W. Witwer is an officer of the International Society for Extracellular Vesicles (ISEV), has served as an advisor for Neurodex and ShiftBio and an ad hoc consultant with NeuroTrauma Sciences, Kineticos, King Abdulaziz University and Burst Biologics, and has held research grants from AgriSciX, Yuvan Research, and Ionis Pharmaceuticals. The remaining authors declare no competing financial interests. Funding Information: Prithu Sundd was supported by NIH‐NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027. Suamya Das was supported by NIH grants R35HL150807, UH3 TR002878 and AHA SFRN35120123. Zhenjia Wang was supported by NIH grant (R01EB027078). Pilar Martín was supported by MCIN‐ISCIII‐Fondo de Investigación Sanitaria grant PI22/01759. Kenneth W. Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 and UH3CA241694. Tianji Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH, NIH‐NHLBI grant R56HL141206 and Chicago Biomedical Consortium Catalyst Award. Eduardo Marbán was supported by NIH R01 HL124074 and HL155346‐01. Funding Information: Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027. Suamya Das was supported by NIH grants R35HL150807, UH3 TR002878 and AHA SFRN35120123. Zhenjia Wang was supported by NIH grant (R01EB027078). Pilar Martín was supported by MCIN-ISCIII-Fondo de Investigación Sanitaria grant PI22/01759. Kenneth W. Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 and UH3CA241694. Tianji Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH, NIH-NHLBI grant R56HL141206 and Chicago Biomedical Consortium Catalyst Award. Eduardo Marbán was supported by NIH R01 HL124074 and HL155346-01. Publisher Copyright: © 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
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