Exosomes have been of great interest in the recent years due to the discovery of their potential in so many research and analytic procedures. Exosomes are known to have some unique functions, such as their ability to alter recipient cell bioactivities, acting like intercellular messengers and also having therapeutic potential in disease diagnostics as well as targeted drug delivery. Improvement in the field of nanotechnology, has opened several paths for the growth of exosomes in therapeutics. The major advantages of using exosomes in therapeutics are that they can easily enter the respective organs, showing best results even in the weakened immune system and can be stored for longer period of time, owing to their greater life span.
Exosome Biogenesis Exosomes are known to arise from the inward folding of the multi-vesicular bodies (MVBs) in order to form the intraluminal vesicles (ILVs). These MVBs are then delivered to the trans-Golgi network (TGN) for the recovery of endosomes and thus, further move to lysosome for degeneration of all the carried substances. The most essential component of exosome biogenesis is the formation of endosomal-sorting complex required for transport (ESCRT).
The ESCRT consists of four complexes namely ESCRT‐0, ESCRT‐I, ESCRT‐II, and ESCRT‐III. The two types of pathways involved in exosomal formation are described below:
ESCRT-dependent pathway- In ESCRT-dependent pathway, ESCRT‐0 commences its pathway by capturing the ubiquitinated proteins that are concealed in the endosome. Both ESCRT‐I and ESCRT‐II are involved in sorting these ubiquitinated proteins. ESCRT‐II is involved in synchronizing the gathering of ESCRT‐III, that is further responsible for causing the splitting of vesicles from the membrane. Thus, it paves the way for another cycle of biogenesis.
ESCRT-independent pathway- In ESCRT-independent pathway, lipids such as waxy lipid molecules and sphingomyelinases are involved in the formation of MVBs. Along with these lipids, tetraspanins are also involved in this pathway.
Manufacturing of Exosomes
Exosomes are known to be allocated in cellular systems due to which they act as medium of information as well as material transmission. Although, exosomes are considered as the intermediary of various intercellular communications yet difficulties for accurate isolation and manufacturing of exosomes is still prevalent. The possible reason behind this includes lack of understanding between exosome characteristic and function, and shortage of scalable solutions to separate specific exosomes. Therefore, the characteristics of exosomes should be monitored closely to ensure high-quality and stable finished product. In addition, several analytical techniques are being used to determine exosome characteristics. Also, appropriate exosome manufacturing platforms are required to improve their advancement as a new therapeutic tool.
Challenges Associated with the Development and Manufacturing of Exosomes
Although recent studies have shown encouraging advances in the exosome related therapeutics, however there are several challenges which severely hinder further development and manufacturing of exosomes.
Therapeutic Applications of Exosomes
In addition to their roles in pathophysiological processes and diagnostic evaluations, recently, several studies have applied exosomes to design novel therapeutic applications.
Future Opportunities for Exosomes and their Therapeutics
Exosomes-based therapeutics have generated enthusiasm within the medical science community, thereby, defining a new frontier in regenerative medicine. The advantages offered by them, including low immunogenicity, high targeting ability, enhanced circulating ability and crossing blood-brain-barrier make them suitable to be used in therapeutics. Several recent studies show that the exosomes could be used as an appropriate biomarker or vector of various potential therapeutic molecules, representing a theranostic approach. It is a relatively newer field, focused on building systems with the application of diagnosis as well as therapy, together.
For more details on this emerging domain, check out the following report: