Boosting Extracellular Vesicle Secretion

Overview

Journal Biotechnol Adv

Specialties Biochemistry
Biotechnology

Date 2022 May 19

PMID 35588952

Authors

Lior Debbi

Shaowei Guo

Dina Safina

Shulamit Levenberg

Affiliations

Soon will be listed here.

Abstract

In recent years, extracellular vesicles (EVs), specifically exosomes, have emerged as a promising strategy for treating a wide spectrum of pathologies, such as cancer and COVID-19, as well as promoting tissue regeneration in various conditions, including cardiomyopathies and spinal cord injuries. Despite the great potential of EV-based therapies, poor yield and unscalable production of EVs remain big challenges to overcome to translate these types of treatment to clinical practices. Here, we review different strategies for enhancing EV yield by physical, biological or chemical means. Some of these novel approaches can lead to about 100-fold increase in EV production yield, thus bringing closer the clinical translation with regard to scalability and efficiency.

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References

Fan J, Lee C, Kim S, Chen C, Aghaloo T, Lee M . Generation of Small RNA-Modulated Exosome Mimetics for Bone Regeneration. ACS Nano. 2020; 14(9):11973-11984. PMC: 7530137. DOI: 10.1021/acsnano.0c05122. View

Ban J, Lee M, Im W, Kim M . Low pH increases the yield of exosome isolation. Biochem Biophys Res Commun. 2015; 461(1):76-9. DOI: 10.1016/j.bbrc.2015.03.172. View

Piffoux M, Silva A, Lugagne J, Hersen P, Wilhelm C, Gazeau F . Extracellular Vesicle Production Loaded with Nanoparticles and Drugs in a Trade-off between Loading, Yield and Purity: Towards a Personalized Drug Delivery System. Adv Biosyst. 2020; 1(5):e1700044. DOI: 10.1002/adbi.201700044. View

Guo S, Debbi L, Zohar B, Samuel R, Arzi R, Fried A . Stimulating Extracellular Vesicles Production from Engineered Tissues by Mechanical Forces. Nano Lett. 2021; 21(6):2497-2504. DOI: 10.1021/acs.nanolett.0c04834. View

Zhu J, Lu K, Zhang N, Zhao Y, Ma Q, Shen J . Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way. Artif Cells Nanomed Biotechnol. 2017; 46(8):1659-1670. PMC: 5955787. DOI: 10.1080/21691401.2017.1388249. View

Gonzalez-King H, Garcia N, Ontoria-Oviedo I, Ciria M, Montero J, Sepulveda P . Hypoxia Inducible Factor-1α Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes. Stem Cells. 2017; 35(7):1747-1759. DOI: 10.1002/stem.2618. View

Pinto A, Marangon I, Mereaux J, Nicolas-Boluda A, Lavieu G, Wilhelm C . Immune Reprogramming Precision Photodynamic Therapy of Peritoneal Metastasis by Scalable Stem-Cell-Derived Extracellular Vesicles. ACS Nano. 2021; 15(2):3251-3263. DOI: 10.1021/acsnano.0c09938. View

Ambattu L, Ramesan S, Dekiwadia C, Hanssen E, Li H, Yeo L . High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism. Commun Biol. 2020; 3(1):553. PMC: 7536404. DOI: 10.1038/s42003-020-01277-6. View

Perets N, Hertz S, London M, Offen D . Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Mol Autism. 2018; 9:57. PMC: 6249852. DOI: 10.1186/s13229-018-0240-6. View

10.

Miller C, Bondurant B, McLean S, McGovern K, OBrien D . Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry. 1998; 37(37):12875-83. DOI: 10.1021/bi980096y. View

11.

Liu W, Li L, Rong Y, Qian D, Chen J, Zhou Z . Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 2019; 103:196-212. DOI: 10.1016/j.actbio.2019.12.020. View

12.

Shao C, Yang F, Miao S, Liu W, Wang C, Shu Y . Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018; 17(1):120. PMC: 6087002. DOI: 10.1186/s12943-018-0869-y. View

13.

Almeria C, Weiss R, Roy M, Tripisciano C, Kasper C, Weber V . Hypoxia Conditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Induce Increased Vascular Tube Formation . Front Bioeng Biotechnol. 2019; 7:292. PMC: 6819375. DOI: 10.3389/fbioe.2019.00292. View

14.

Paolicelli R, Bergamini G, Rajendran L . Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia. Neuroscience. 2018; 405:148-157. DOI: 10.1016/j.neuroscience.2018.04.003. View

15.

Fukuda S, Kita S, Obata Y, Fujishima Y, Nagao H, Masuda S . The unique prodomain of T-cadherin plays a key role in adiponectin binding with the essential extracellular cadherin repeats 1 and 2. J Biol Chem. 2017; 292(19):7840-7849. PMC: 5427265. DOI: 10.1074/jbc.M117.780734. View

16.

Turturici G, Tinnirello R, Sconzo G, Geraci F . Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. Am J Physiol Cell Physiol. 2014; 306(7):C621-33. DOI: 10.1152/ajpcell.00228.2013. View

17.

Zeng Z, Zhao Y, Chen Q, Zhu S, Niu Y, Ye Z . Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis. Oncogene. 2021; 40(36):5505-5517. DOI: 10.1038/s41388-021-01960-w. View

18.

Vanlandingham P, Ceresa B . Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. J Biol Chem. 2009; 284(18):12110-24. PMC: 2673280. DOI: 10.1074/jbc.M809277200. View

19.

Tse S, Tan C, Park J, Gnanasekaran J, Gupta N, Low J . Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles. Cancers (Basel). 2020; 12(10). PMC: 7601203. DOI: 10.3390/cancers12102917. View

20.

Obata Y, Kita S, Koyama Y, Fukuda S, Takeda H, Takahashi M . Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release. JCI Insight. 2018; 3(8). PMC: 5931116. DOI: 10.1172/jci.insight.99680. View