Extracellular Vesicle: Exosomes can be the Key to Understand Incurable Disease

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You have heard of mitochondria, nucleus, and ribosomes. But what about extracellular vesicles or exosomes? This less famous organelle can actually be the important missing link in understanding cancer and other deadly diseases.

Introduction to Extracellular Vesicle

Extracellular vesicles (EVs) used to be poorly understood and overlooked. However, it´s now a hot topic in the scientific world. What are EVs? To put it simply, vesicle refers to small structures which contain liquid and enclosed a lipid bilayers.

Extracellular indicates that the vesicle is located outside the cell. EVs are secreted by cells (exocytosis) to the extracellular space and contains biological molecules like protein. They are also taken up by other cells through endocytosis.

There are three types of EVs: Exosome, Microvesicles, and Apoptotic body. Apoptotic body is released from dead cells (apoptosis). On the other hand, exosomes and Microvesicles are released from healthy cells. Abcam has summarized their differences in the following table:

  Exosomes Microvesicles Apoptotic bodies
Origin Endocytic Pathway Plasma Membrane Plasma Membrane
Size 40-120 nm 50 – 1,000 nm 500 – 2,000 nm
Function Intercellular communication Intercellular communication Facilitate phagocytosis
Content Proteins and nucleic acids (mRNA, miRNA and other non-coding RNAs) Proteins and nucleic acids (mRNA, miRNA and other non-coding RNAs) Nuclear fractions, cell organelles

 

The interest in EVs, particularly exosomes, is growing massively. A study conducted by Wei and colleagues in 20161 showed that research paper about exosomes increased exponentially since 2007.

What caused this sudden rise in popularity? EVs´ prominent role is to facilitate communication between cells (intercellular communication), which includes delivering or eliminating cellular component. However, it is discovered that exosomes are involved in diseases propagation, including cancer. Is this the sole reason for EVs sudden fame though?

Exosomes in the medical world, Friends or Foe?

So, what are exosomes´ role in diseases propagation? When secreted by healthy cells, exosomes contain active biological molecule for other cells. Unfortunately, exosomes also spread pathological misfolded proteins, triggering several neurodegenerative diseases such as alzheimer2, Huntington diseases, and amyotrophic lateral sclerosis (ALS)3.

More importantly, Steinbichler and co-workersfrom the Medical University of Innsbruck, Austria, have found that exosomes are involved in every step of cancer growth and development. Thus, understanding EVs is a precious link to discover new facts about these famous diseases. But, is it all about exosomes?

Turns out ´fight poison with poison’ seems to be an ideal description for exosomes. While it is found to be one of the bad guys, scientists also found the good side of exosome: as an effective drug delivery method.

Nano-sized particles like exosome have exceptional drug delivery ability, as explained in our previous article. Furthermore, because exosomes are naturally produced by our body, it is less likely to be cytotoxic5. A perfect candidate for alternative drug delivery!

Exosomes potential in clinical practice does not stop there. It is also found that the cell of sick patient secreted exosomes with different content (especially protein and genetic material) than of healthy person. Moreover, the content also different from diseases to diseases6. Thus, exosomes have huge potential as biomarkers, which will be valuable for early diagnosis of fatal diseases.

However, the best results do not come without big challenges. The main challenge in commercializing EVs for clinical purposes lays in the characterization.

Unfortunately, Scientist still encounters difficulty in discriminating between exosomes and microvesicles. Their differences in properties such as size, morphology, and protein composition are still deemed insufficient for a clear distinction7. Furthermore, the proper nomenclature for EVs is still on the ongoing debate between scientists. Many papers even use EVs and exosomes term interchangeably.

We still need to dig deeper into the molecular level to accurately characterize all EVs into the correct group. Moreover, characterization of EVs will also give us a deeper understanding of their potential and behavior.

ZetaView: Seeing is Believing

As researcher compete to fully understand EVs, one particular nanoparticle tracking analyzer (NTA) seems to be a primadonna for EVs characterization. This equipment, ZetaView by Particle Metrix, has gained huge popularity within Cambridge University community. Andreas Baur, a scientist from University Hospital of Erlangen in Germany, also praised ZetaView ability.

What makes the ZetaView stand out? According to Baum, ZetaView is the only NTA that can accurately quantify the exact number of nanoparticle exosomes in solutions.

In addition to that, ZetaView also gives the basic physical information (i.e. size and zeta potential) and allow determination of low concentration particle.

Another plus point is that this equipment is easy to use. Trying to understand EVs is already a mental task, operating a not user-friendly tool is definitely the last thing you want.

Michael Jones, CEO of CellGS in the UK also added that high sample throughput of ZetaView is especially valuable for a commercial laboratory.

In conclusion, understanding EVs are our precious link to finally fathom cancer and neurodegenerative diseases. Potentially even finding the cure! Even though we are still in progress to achieve better EVs characterization, ZetaView is proven to have helped EVs research considerably. It might not too long until scientist can fully master everything about EVs.

We at Solmeglas, are proud to bring ZetaView to Spanish and Portuguese scientific community. We will be attending ISEV 2018 conference in Barcelona alongside our partner, Particle Metrix. Say hello and receive free ZetaView demonstration by our expert team! Alternatively, please don´t hesitate to contact us.

References

  1. Wei, X, Shao, J, Zhao, J, Chen, Z, Bai, Y, Li, M, Zhai, X, Wang, Y, Wang, N, Wang, Y, Wang, Q, & Zhang, Z n.d., ‘Global scientific trends on exosome research during 2007-2016: a bibliometric analysis’, Oncotarget, 8, 29, pp. 48460-48470
  2. Xiao, T, Zhang, W, Jiao, B, Pan, C, Liu, X, & Shen, L 2017, ‘The role of exosomes in the pathogenesis of Alzheimer’ disease’, Translational Neurodegeneration, 1
  3. Howitt, J, & Hill, A n.d., ‘Exosomes in the Pathology of Neurodegenerative Diseases’, Journal Of Biological Chemistry, 291, 52, pp. 26589-26597
  4. Steinbichler, T, Dudás, J, Riechelmann, H, & Skvortsova, I 2017, ‘The role of exosomes in cancer metastasis’, Seminars In Cancer Biology, 44, pp. 170-181
  5. EL Andaloussi, S, Mäger, I, Breakefield, X, & Wood, M 2013, ‘Extracellular vesicles: biology and emerging therapeutic opportunities’, Nature Reviews. Drug Discovery, 12, 5, pp. 347-357
  6. Barile, L, & Vassalli, G 2017, ‘Exosomes: Therapy delivery tools and biomarkers of diseases’, Pharmacology And Therapeutics, p. 63
  7. Bobrie, A, Colombo, M, Raposo, G, & Théry, C 2011, ‘Exosome Secretion: Molecular Mechanisms and Roles in Immune Responses’, Traffic, vol. 12, no. 12, pp. 1659-1668
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