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

Anika Nagelkerke; Miina Ojansivu; Luke van der Koog; Thomas E Whittaker; Eoghan M Cunnane; Andreia M Silva; Niek Dekker; Molly M Stevens

doi:10.1016/j.addr.2021.04.013

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

Adv Drug Deliv Rev. 2021 Aug:175:113775. doi: 10.1016/j.addr.2021.04.013. Epub 2021 Apr 17.

Authors

Anika Nagelkerke¹, Miina Ojansivu², Luke van der Koog³, Thomas E Whittaker⁴, Eoghan M Cunnane⁵, Andreia M Silva⁶, Niek Dekker⁷, Molly M Stevens⁸

Affiliations

¹ Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, P.O. Box 196, XB20, 9700 AD Groningen, the Netherlands. Electronic address: a.p.nagelkerke@rug.nl.
² Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. Electronic address: miina.ojansivu@ki.se.
³ Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, P.O. Box 196, XB10, 9700 AD Groningen, the Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: l.van.der.koog@rug.nl.
⁴ Department of Materials, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK; Institute of Biomedical Engineering, Imperial College London, London, UK.
⁵ Department of Materials, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK; Institute of Biomedical Engineering, Imperial College London, London, UK. Electronic address: e.cunnane@imperial.ac.uk.
⁶ Discovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Electronic address: andreia.silva@astrazeneca.com.
⁷ Discovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Electronic address: niek.dekker@astrazeneca.com.
⁸ Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Materials, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK; Institute of Biomedical Engineering, Imperial College London, London, UK. Electronic address: m.stevens@imperial.ac.uk.

PMID: 33872693
DOI: 10.1016/j.addr.2021.04.013

Abstract

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.

Keywords: Clinical trial; EV engineering; EV-functionalized biomaterials; Mesenchymal stem cells; Regenerative medicine; Therapeutic cargo delivery.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Drug Delivery Systems / methods*
Extracellular Vesicles / physiology*
Humans
Regenerative Medicine / methods*
Tissue Engineering / methods*

Grants and funding

MR/R015651/1/MRC_/Medical Research Council/United Kingdom