Putting exosomes under the commercial microscope

Author: Ali Ranjbaran, Editor: Dr Chih Wei Teng

Progress in medical science has always been driven by the need to overcome challenges and new threats to public health. Some of these challenges arise as a result of the evolution of disease and virus, others simply exist beyond our understanding and current state of the art technology. Taken at any snapshot in time, current treatments of the day such as surgery, transplantation, and medication which have been routine treatment for many years, seem to be inadequate to address the global burden of the diseases (1). For example, organ transplantation is plagued by limited donor supply, high costs, immune rejection, and often need for lifelong chronic immunosuppressant therapy. Current pursuits include tissue regeneration refers to the physiological processes that necrotic cells and tissue are replaced by healthy cells and newly formed healthy tissue (2). The strategies for promoting tissue regeneration mainly include stem cell therapy, gene therapy, and tissue engineering, all of which can be classified under the broad definition of regenerative medicine. In the last decade, the capabilities of stem cells offered much potential in tissue regeneration, treating damaged caused by cardiovascular diseases and diabetes, such as corneal blindness and ulcers.

Despite the advantages of cell based therapies, some challenges remain. These include clinical risks (such as inflammation, the possibility of the immune response, and virus contamination), manufacturing costs, and regulation issues. As a consequence, clinicians and companies may elect to seek alternative therapies with similar outcomes but fewer risks and challenges rather than investing in cellular therapies. One such alternatives are exosomes, also referred to as intraluminal vesicles (ILVs) are a subtype of Extracellular Vesicles (EVs)- typically 30–150 nm in diameter (3). Originally thought of as cellular dumping or a way for cells to get rid of unneeded or unwanted material, it has been found that exosomes participate in cell-cell communication, cell maintenance, and tumour progression because of the DNAs, RNAs, proteins, and other bioactive signals carried in EVs.

Recent studies have demonstrated that the biological activities of EVs are similar to that of their source cells (2). As stem cells have been widely applied in the regenerative medicine field, EVs from stem cells with similar biological properties to their source stem cells may present a novel option of an alternative therapeutic option or delivery mechanism in the field of regenerative medicine. A recent spotlight by Cade Hildreth on exosomes gave examples of biotechs specialising in exosomes to include Exopharm and Vivazome Therapeutics in Australia and Capricor Therapeutics from the US.

Although exosomes seem promising, more standardized methods for exosome isolation and analysis are needed to meet the regulatory requirements of the FDA and other regulatory agencies to use exosomes as biomarkers, vaccines, drug delivery devices, and therapeutic tools.

This article is the first in a series of blogs about exosomes from a business perspective. The table below presents a quick comparison between exosomes and stem cell therapies. While at the outset, it seems that exosomes present an advantage over cell therapies, we must understand that we have only started to peel back the layers of understanding. As with novel techniques and therapies, there is often a lack of established protocol and in the case of exosomes, challenges associated with its small size, e.g. isolation. No doubt the information in the table will change as our knowledge of exosome grows and when exosomes are put into practice. More investigation needed. This table further presents the themes for future blogs, with the next being a look into the differences in sourcing and manufacture of exosomes and stem cell therapies.

Exosomes Cell Therapy
Safety:

·      Contamination

·      Inflammation2

·      Immune rejection2,4

·      Vascular obstructive effect4

·      Microvascular thrombosis4

·      Tumour formation2,4

No

No

No

No

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Cost:

·      Application

·      Manufacture2

Cheap

Cheap

Expensive

Expensive

Manufacturing:

·      Process

·      Size2

·      Stability2

·      Storage2

Simple to complex

Very small

High

Simple

Complex and difficult

Varies

Low

Complex

Origin/type5 Autologous, Allogenic, Xenogeneic

Embryonic, mesenchymal,

cancer stem cells

Origin (age) dependent risks Moderate High
Medical application Simple (IV) Requires hospitalization
Market (product) Off the shelf Requires hospitalization

 Reference:

  1. Sang Ging Ong (2015, Circulation Research)
  2. Zhijie Ma (2020, Biomicrofluidics)
  3. Laura M. Doyle (2019, Cells)
  4. Poornima Venkat (2018, Stem cells translational medicine)
  5. Oh Young Bang (2019, Frontiers in neurology)