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Exploring Exosome Research: Answering Your Questions About the “Next Small Thing”

By 12.07.2021

Many biomedical researchers spend their careers searching for big discoveries – the next wonder drug, vaccine, or device that’s going to solve the greatest challenges in modern medicine.

But many monumental findings have small beginnings, routed in foundational R&D and a genuine curiosity about basic biology. Just look at the history of Nobel Prize-worthy discoveries, such as CRISPR-Cas or GFP: These discoveries are, at first, not appreciated for the dramatic, long-term impact that they end up having on biotechnology and medicine.1,2

Well, allow me to introduce you to biology’s next great example of this – the exosome – which has the potential to alter the behavior of or even eliminate cancer cells, cardiac scars, or neurodegenerative disorders.3,4

Upon initial inspection, exosomes are quite unremarkable. They are phospholipid-enclosed sacks, about 100 nm in diameter, that carry bioactive materials from one cell to another. Yep, the next earth-shattering revelation in medicine is about as sophisticated as a trash bag. Until fairly recently, immunologists studying exosomes as part of allergy research thought exosomes removed cellular waste products, and their contents were therefore little more than cellular throwaways.5 A closer look, however, reveals what has scientists from virtually every field of biomedical research excited about exosomes’ diagnostic and therapeutic potential.

Watch episode 1 of our mini-series exploring Exosomes – the next small thing. Leading scientists discuss how exosomes are tiny vesicles containing complex RNA and protein cargo. Cargo that could be the key to the next be breakthrough in their research.

Exosomes are more than a cells waste removal system.

Exosomes may seem like trivial parts of a cell’s waste removal system, but the true value of exosomes lies in the cargo they carry, RNA and protein.6 Nearly fifteen years ago, researchers discovered that exosomes contain genetic material – microRNAs which happen to play a huge regulatory role in gene expression in our cells.7,8 Far from being cellular trash, these vesicles are part of a massively complex biological communication system.

Traditionally, cells have been known to communicate with other cells via either paracrine (chemical), endocrine (hormone), or synaptic (electrophysiological) mechanisms. Adding a fourth cellular communication mechanism is potentially a game-changer in several fields, as this would allow the targeted delivery of gene therapies or other therapeutics, with implications in many therapeutic areas, including cardiac repair to Parkinson’s treatment.10,11

Exosomes are about as close as we can get to the perfect diagnostic and therapeutic vehicle.  They are immune-privileged, evading recognition and destruction by the immune system, thus limiting any potential immune-related safety issues.12 Many types of exosomes can permeate different tissue types, including the blood-brain barrier.13 That feature alone could make exosome delivery a feasible treatment course for brain cancers which are notoriously difficult to access and treat pharmacologically.  It is also possible to use the type and contents of exosomes to diagnose diseases at an earlier stage (compared to traditional biopsy), determine the presence of certain tumor types, and track treatment efficacy, all from a simple serum sample.14

Exosomes Can Expedite Cancer and Facilitate Infections

Exosomes can also work against us, allowing cancerous tumors to evade immune cells or accelerating metastasis and increasing resistance to chemotherapy.15 Exosomes may also promote the cell-to-cell spread of pathogens, trafficking infectious material from cell to cell, safe from the immune system.16 While not great for human physiology, exosomes’ incredible delivery powers could be harnessed for good.

Episode 3 dives into the indicators exosomes can show when trying to identify signs of normalcy or malignancy in cells. Learn about products developed to simplify the overall study of exosomes and cancer.

Exploring the biology of extracellular vesicles (EVs) and their potential use in clinical applications has gained considerable interest over the last several yearsHere we present an automated system for the isolation of EVs for further downstream protein analysis using Invitrogen™ Dynabeads™ magnetic beads and the Thermo Scientific™ KingFisher™ Flex instrument.

 

Uncovering More about Intact Exosomes with New Tools

While we now know that exosomes can deliver microRNAs and proteins from one cell to another, researchers are just beginning to scratch the surface of these tiny vesicles’ potential.17 Innumerable questions remain about their function and applications. In theory, it should be possible to block the secretion of damaging exosomes, imitate beneficial ones, or package life-saving drugs within them. But these tiny sacks are as complex and heterogeneous as the humans who study them and exosomes haven’t relinquished their secrets easily. As a result, the scientific world is focusing more on exosome research. The NIH is currently in Phase II of a $130 million investment in exosomes, focusing on tools, technologies, and methods for understanding extracellular vesicles.18

Exosomes could be critical to our understanding of and approach to treating myriad diseases, but only with the proper tools to probe their impact. Thermo Fisher Scientific has a variety of specialized products made specifically for the extraction and isolation of exosomes. The Total Exosome RNA & Protein Isolation Kit can extract intact exosomes, ready for endpoint analysis or in vivo studies. This kit is simple and versatile. Users can isolate both protein and RNA from cell culture media, serum, saliva, plasma, urine, and many other sample types. The sample is incubated overnight, and our proprietary isolation reagent pulls exosomes out of solution, where they can be recovered by centrifugation.

From there, Dynabeads™ can be used to isolate and quantify your exosomes of interest. When coupled with the KingFisher™ platform, Dynabeads’ immunomagnetic separation processes can be automated, allowing for high-throughput purification of exosome subpopulations.

The possibilities and applications of exosomes seem limitless. They present an unparalleled diagnostic and therapeutic approach to cancer, diabetes, heart disease, Alzheimer’s, and more.19-21 But much remains to be learned about these incredible vesicles. As we continue to understand more about how exosomes function and how they can be utilized to deliver life-saving treatments, the impact of the next small thing in biomedical research will only grow.

Find out how we are driving exosome research forward, with our portfolio of exosome products.

This article is for Research Use Only. Not for use in diagnostic procedures.

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References

  1. A Brief History of CRISPR-Cas9 Genome-Editing Tools. BiteSizeBio website: https://bitesizebio.com/47927/history-crispr/. Published June 30, 2020. Accessed June 21, 2021.

  2. Sanders JK, Jackson SE. The discovery and development of the green fluorescent protein, GFP. Chem Soc Rev. 2009;38(10):2821-2822.

  3. Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of Exosome Composition. Cell. 2019;177(2):428-445.e18.

  4. Marsh SR, Williams ZJ, Pridham KJ, Gourdie RG. Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine. J Cardiovasc Dev Dis. 2021;8(5):52.

  5. Hough KP, Deshane JS. Exosomes in Allergic Airway Diseases. Curr Allergy Asthma Rep. 2019;19(5):26.

  6. Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470-1476.

  7. Zhou R, Chen KK, Zhang J, et al. The decade of exosomal long RNA species: an emerging cancer antagonist. Mol Cancer. 2018;17(1):75.

  8. O’Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402.

  9. Different Types of Cellular Communication. Sciencing website: https://sciencing.com/different-types-cellular-communication-7631508.html. Published May 6, 2019. Accessed July 27, 2021.

  10. Kishore R, Khan M. More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. Circ Res. 2016;118(2):330-343.

  11. Sarko DK, McKinney CE. Exosomes: Origins and Therapeutic Potential for Neurodegenerative Disease. Front Neurosci. 2017;11:82.

  12. Milosevits G, Szebeni J, Krol S. Exosomes: potential model for complement-stealth delivery systems. Eur J Nanomedicine. 2015;7:207–218.

  13. Chen CC, Liu L, Ma F, et al. Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro. Cell Mol Bioeng. 2016;9(4):509-529.

  14. Madhavan B, Yue S, Galli U, et al. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer. 2015;136(11):2616-2627.

  15. Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell. 2019;49(3):347-360.

  16. Schorey JS, Bhatnagar S. Exosome function: from tumor immunology to pathogen biology. Traffic. 2008;9(6):871-881.

  17. Huda MN, Nafiujjaman M, Deaguero IG, et al. Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications. ACS Biomater Sci Eng. 2021;7(6):2106-2149.

  18. ExRNA Communication Funding Information. National Center for Advancing Translational Sciences website:https://ncats.nih.gov/exrna/funding. Published September 22, 2020. Accessed July 28, 2021.

  19. Chang W, Wang J. Exosomes and Their Noncoding RNA Cargo Are Emerging as New Modulators for Diabetes Mellitus. Cells. 2019;8(8):853.

  20. New Virginia Tech startup seeks to use nano-capsules derived from milk to deliver heart drug. Virginia Tech website: https://vtx.vt.edu/articles/2020/02/new-virginia-tech-startup-seeks-to-use-nano-capsules-derived-fro.html. Published February 12, 2020. Accessed July 28, 2021.

  21. Cai ZY, Xiao M, Quazi SH, Ke ZY. Exosomes: a novel therapeutic target for Alzheimer’s disease?. Neural Regen Res. 2018;13(5):930-935.

 

 

 

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