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

Guoping Li; Tianji Chen; James Dahlman; Lola Eniola-Adefeso; Ionita C Ghiran; Peter Kurre; Wilbur A Lam; Jennifer K Lang; Eduardo Marbán; Pilar Martín; Stefan Momma; Malcolm Moos; Deborah J Nelson; Robert L Raffai; Xi Ren; Joost P G Sluijter; Shannon L Stott; Gordana Vunjak-Novakovic; Nykia D Walker; Zhenjia Wang; Kenneth W Witwer; Phillip C Yang; Martha S Lundberg; Margaret J Ochocinska; Renee Wong; Guofei Zhou; Stephen Y Chan; Saumya Das; Prithu Sundd

doi:10.1002/jev2.12305

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

J Extracell Vesicles. 2023 Feb;12(2):e12305. doi: 10.1002/jev2.12305.

Authors

Guoping Li¹, Tianji Chen², James Dahlman³, Lola Eniola-Adefeso⁴, Ionita C Ghiran⁵, Peter Kurre⁶, Wilbur A Lam⁷, Jennifer K Lang⁸, Eduardo Marbán⁹, Pilar Martín¹⁰, Stefan Momma¹¹, Malcolm Moos¹², Deborah J Nelson¹³, Robert L Raffai^{14

15}, Xi Ren¹⁶, Joost P G Sluijter¹⁷, Shannon L Stott¹⁸, Gordana Vunjak-Novakovic¹⁹, Nykia D Walker²⁰, Zhenjia Wang²¹, Kenneth W Witwer²², Phillip C Yang²³, Martha S Lundberg²⁴, Margaret J Ochocinska²⁵, Renee Wong²⁴, Guofei Zhou²⁶, Stephen Y Chan^{27

28}, Saumya Das¹, Prithu Sundd^{27

29}

Affiliations

¹ Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
² Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
³ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia, USA.
⁴ Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Anesthesia and Pain Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts, USA.
⁶ Children's Hospital of Philadelphia, Comprehensive Bone Marrow Failure Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Wallace H. Coulter Department of Biomedical Engineering, Department of Pediatrics, Emory School of Medicine, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University and Georgia Institute of Technology, Atlanta, Georgia, USA.
⁸ Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Veterans Affairs Western New York Healthcare System, Buffalo, New York, USA.
⁹ Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁰ Centro Nacional de Investigaciones Cardiovasculares (CNIC), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
¹¹ Institute of Neurology (Edinger Institute), University Hospital, Goethe University, Frankfurt am Main, Germany.
¹² Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
¹³ Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, Illinois, USA.
¹⁴ Department of Veterans Affairs, Surgical Service (112G), San Francisco VA Medical Center, San Francisco, California, USA.
¹⁵ Department of Surgery, Division of Vascular and Endovascular Surgery, University of California, San Francisco, California, USA.
¹⁶ Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
¹⁷ Department of Experimental Cardiology, Circulatory Health Laboratory, Regenerative Medicine Centre, UMC Utrecht, University Utrecht, Utrecht, The Netherlands.
¹⁸ Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
¹⁹ Department of Biomedical Engineering, Department of Medicine, Columbia University, New York, New York, USA.
²⁰ Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, USA.
²¹ Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA.
²² Department of Molecular and Comparative Pathobiology, Department of Neurology and Neurosurgery, and The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²³ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
²⁴ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
²⁵ Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
²⁶ Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
²⁷ Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
²⁸ Division of Cardiology and Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
²⁹ Division of Pulmonary Allergy and Critical Care Medicine and Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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.

Keywords: Heart, lung, blood and sleep (HLBS) diseases; extracellular vesicles (EVs); therapeutics and diagnostics.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cell Communication
Extracellular Vesicles* / metabolism
Lung / metabolism
Nucleic Acids* / metabolism
Sleep
Vereinigte Staaten

Substances

Nucleic Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding