Exosomes represent one form of extracellular vesicles (EVs) produced naturally from all cells within the body. While exosomes have been studied for decades; our understanding of their biological function was limited to their potential role as cellular disposal systems. Seminal findings reported in 2007 unveiled the role of exosomes and other EVs as shuttles for intercellular communication. These discoveries paved the way for studies of exosomes beyond basic biomedical research, introducing this class of biologics for translational research leading to clinical applications ranging from biomarkers to therapeutics of human disease.
Because exosomes carry various payloads encapsulated within a lipid bilayers, they protect the biological messages from nonspecific binding to extracellular matrix or serum proteins, preventing their rapid clearance by host immune system or enzymatic degradation by proteases or nucleases abundant in the serum or interstitial fluids. These features confer a great advantage for exosomes to serve as both biomarkers that can preserve the unique signatures of pathological conditions in various biological fluids and drug delivery vehicles that can deliver protective cargo efficiently to target cells or tissues. Their ability to deliver intraluminal cargo in stealth modes endows exosomes with a perfect analogy as “Trojan Horses” for drug delivery. Moreover, naïve exosomes derived from various types of stem cells are recognized to exert the majority of the therapeutic potential ascribed to stem cell therapy and, not surprisingly are regarded as next generation cell-free cell therapeutics.
Despite recent advances in exosome biology, numerous questions remain to be addressed. Indeed, although exosome-based therapeutics are generally regarded as safe and biocompatible, their long-term safety and immunogenicity are not fully determined. Their obscure mode of actions makes it difficult to establish proper pharmacodynamic models and predicting adverse effects for exosome therapeutics. The heterogeneity of exosomes, even when manufactured from single clone-derived cell lines poses significant challenges that include quality control, isolation methods, reproducibility, and scalability for production. Furthermore, the biological complexity of exosomes makes their pharmacokinetic analysis extremely challenging. Indeed, chasing only one component of injected exosomes, for example their lipid or protein cargo, likely provides a fraction of whole picture, akin to a blind man’s description of an elephant.
The goal of this Article Collection is to solicit the contribution of articles and findings broadly addressing areas of exosome-based therapeutics and related research including preclinical discovery, clinical and laboratory research, single EV analysis, and manufacturing:
- Characterization of therapeutic effects and adverse responses of exosome-based therapeutics in various preclinical animal models or organ-on-a-chip models.
- Engineering strategies for drug loading and active targeting
- In-depth analysis of immunogenicity and genotoxicity of allogenic exosomes
- Single EV analysis for quality control
