Exosomes – An Introduction

Exosomes are biologically active nanoparticles secreted by cells. They fulfil a range of functions in the human body depending on the type of cells that is secreting them. What Exosomes have in common regardless of source cell is their general mechanism of action.

Exosomes are extra-cellular vesicles that carry molecular cargo: nucleic acids, proteins and lipids – the cellular equivalent of information, machinery and energy.

Exosomes are taken up by other cells where their cargo is unloaded and utilised: the delivered information and machinery is used to re-program the recipient cell, the energy is used to execute the new programme. Especially interesting are Exosomes secreted by stem cells – cells that can potentially develop into many kinds of tissues or organs. Scientific evidence is mounting however, that the main contribution of stem cells towards tissue regeneration is in fact mediated through their Exosomes – by providing information, machinery and energy to drive repair programs in cells of damaged tissues.

The scientific body around the regenerative effects of exosomes suggests a potentially wide area of therapeutic application across disease areas and conditions, also reviewed by the International Society of Extracellular Vesicles (ISEV) (www.isev.org) in 2015 (Lener et al., 2015).

The Science behind Exosomes

Previous therapeutic stem cell-based approaches for organ repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. So far, many stem cell based treatment approaches consisted of “bluntly” injecting stem cells into patients under the overall hypothesis that these “super cells” will engraft in the injured tissue, differentiate to functional organ cells and in this way regenerate the injured organ. However, these approaches have failed to translate into palpable outcomes for patients in clinical trials leading to the conclusion that further research is required to advance this technology. In recent years stem cell theory, however, has progressed and the scientific focus shifted away from the actual cell to the particles secreted by these cells – so called extracellular vesicles or Exosomes. 

Exosomes contain key determinants necessary to maintain stem cell properties and their quantitative reduction or loss may result in cellular differentiation or phenotypic changes (Bauer et al., 2011). Alternatively, they cargo a wide array of biomolecules, including microRNAs, proteins, lipids and genetic material that they can transfer to target cells to influence important differentiated cell functions and even regulate other stem cells in their respective niches. Exosomes from pluripotent embryonic stem cells have been demonstrated to be able to reprogram hematopoietic progenitors and revert them to a more primitive state (M. Z. Ratajczak, Machalinski, Wojakowski, Ratajczak, & Kucia, 2007). Their role as mediators of the effects during cell therapy is demonstrated by their reparative effects in different disease states (Leroyer et al., 2009) including myocardial infarction (Barile et al., 2014; Khan et al., 2015) and by the observation that EV administration can largely recapitulate the benefits of transplanted cells.

 

  • Introduction: Edgar, J. R. (2016). Q&A: What are exosomes, exactly? BMC Biology, 14(1), 46. http://doi.org/10.1186/s12915-016-0268-z
  • Exosomes in Blood / Circulation: Caby, M.-P., Lankar, D., Vincendeau-Scherrer, C., Raposo, G., & Bonnerot, C. (2005). Exosomal-like vesicles are present in human blood plasma. International Immunology, 17(7), 879–887. http://doi.org/10.1093/intimm/dxh267 
  • Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., et al. (2015). Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. Journal of Extracellular Vesicles, 4, 30087. http://doi.org/10.3402/jev.v4.30087
  • Rani, S., Ryan, A. E., Griffin, M. D., & Ritter, T. (2015). Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Molecular Therapy : the Journal of the American Society of Gene Therapy, 23(5), 812–823. http://doi.org/10.1038/mt.2015.44
  • Basu, J., & Ludlow, J. W. (2016). Exosomes for repair, regeneration and rejuvenation. Expert Opinion on Biological Therapy, 16(4), 489–506. http://doi.org/10.1517/14712598.2016.1131976
  • Marote, A., Teixeira, F. G., Mendes-Pinheiro, B., & Salgado, A. J. (2016). MSCs-Derived Exosomes: Cell-Secreted Nanovesicles with Regenerative Potential. Frontiers in Pharmacology, 7, 231. http://doi.org/10.3389/fphar.2016.00231

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