Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions

被引：420

作者：

Gyoergy, Bence ^{[1
,2
,3
,4
]}

Hung, Michelle E. ^{[5
]}

Breakefield, Xandra O. ^{[1
,2
,3
]}

Leonard, Joshua N. ^{[6
]}

机构：

[1] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[5] Northwestern Univ, Interdept Biol Sci Grad Program, Evanston, IL 60208 USA

[6] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chem Life Proc Inst, Dept Chem & Biol Engn, Evanston, IL 60208 USA

来源：

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55 | 2015年 / 55卷

关键词：

exosomes; extracellular RNA; microvesicles; drug delivery; liposomes; gene medicine; gene therapy; mesenchymal stem cells; nanoparticles; OUTER-MEMBRANE VESICLES; CELL-DERIVED EXOSOMES; MESENCHYMAL STROMAL CELLS; DENDRITIC CELLS; T-CELLS; INTERCELLULAR TRANSFER; DOXORUBICIN DELIVERY; PLASMA-MEMBRANE; PROTECT MICE; STEM-CELLS;

D O I：

10.1146/annurev-pharmtox-010814-124630

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury.

引用

页码：439 / 464

页数：26

共 147 条

[1] Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells [J].

Aharon, Anat ;

Tamari, Tal ;

Brenner, Benjamin .

THROMBOSIS AND HAEMOSTASIS, 2008, 100 (05) :878-885

[2] Microvesicle-mediated RNA Molecule Delivery System Using Monocytes/Macrophages [J].

Akao, Yukihiro ;

Iio, Akio ;

Itoh, Tomohiro ;

Noguchi, Shunsuke ;

Itoh, Yuko ;

Ohtsuki, Yoshinori ;

Naoe, Tomoki .

MOLECULAR THERAPY, 2011, 19 (02) :395-399

[3] Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells [J].

Al-Nedawi, Khalid ;

Meehan, Brian ;

Micallef, Johann ;

Lhotak, Vladimir ;

May, Linda ;

Guha, Abhijit ;

Rak, Janusz .

NATURE CELL BIOLOGY, 2008, 10 (05) :619-U24

[4] Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].

Alvarez-Erviti, Lydia ;

Seow, Yiqi ;

Yin, HaiFang ;

Betts, Corinne ;

Lakhal, Samira ;

Wood, Matthew J. A. .

NATURE BIOTECHNOLOGY, 2011, 29 (04) :341-U179

[5] Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury [J].

Arslan, Fatih ;

Lai, Ruenn Chai ;

Smeets, Mirjam B. ;

Akeroyd, Lars ;

Choo, Andre ;

Aguor, Eissa N. E. ;

Timmers, Leo ;

van Rijen, Harold V. ;

Doevendans, Pieter A. ;

Pasterkamp, Gerard ;

Lim, Sai Kiang ;

de Kleijn, Dominique P. .

STEM CELL RESEARCH, 2013, 10 (03) :301-312

[6] Heparin blocks transfer of extracellular vesicles between donor and recipient cells [J].

Atai, Nadia A. ;

Balaj, Leonora ;

van Veen, Henk ;

Breakefield, Xandra O. ;

Jarzyna, Peter A. ;

Van Noorden, Cornelis J. F. ;

Skog, Johan ;

Maguire, Casey A. .

JOURNAL OF NEURO-ONCOLOGY, 2013, 115 (03) :343-351

[7] Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion [J].

Atay, Safinur ;

Banskota, Samagya ;

Crow, Jennifer ;

Sethi, Geetika ;

Rink, Lori ;

Godwin, Andrew K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (02) :711-716

[8] Syndecan-syntenin-ALIX regulates the biogenesis of exosomes [J].

Baietti, Maria Francesca ;

Zhang, Zhe ;

Mortier, Eva ;

Melchior, Aurelie ;

Degeest, Gisele ;

Geeraerts, Annelies ;

Ivarsson, Ylva ;

Depoortere, Fabienne ;

Coomans, Christien ;

Vermeiren, Elke ;

Zimmermann, Pascale ;

David, Guido .

NATURE CELL BIOLOGY, 2012, 14 (07) :677-685

[9] Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences [J].

Balaj, Leonora ;

Lessard, Ryan ;

Dai, Lixin ;

Cho, Yoon-Jae ;

Pomeroy, Scott L. ;

Breakefield, Xandra O. ;

Skog, Johan .

NATURE COMMUNICATIONS, 2011, 2

[10] Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors [J].

Bartlett, JS ;

Wilcher, R ;

Samulski, RJ .

JOURNAL OF VIROLOGY, 2000, 74 (06) :2777-2785

← 1 2 3 4 5 6 7 8 9 10 →