The Definitive Guide to Exosome Therapy

What are Exosomes?

Exosomes are of general interest for their role in cell biology, and for their potential therapeutic and diagnostic applications. It was originally thought that exosomes were simply cellular waste products, however their function is now known to extend beyond waste removal.

Exosomes are a subset of extracellular vesicles (EVs) surrounded by a lipid bilayer membrane and contain various proteins, RNAs, DNAs, and bioactive lipids that can be transferred between cells. Exosomes are not exclusive to stem cells and are released by many cells throughout the body. They greatly contribute to the improvement of neurodegenerative diseases, diabetes, kidney diseases, osteoporosis and atherosclerotic cardiovascular disease.

Nevertheless, they are important in cell-to-cell communication to control multiple biological processes such as cellular proliferation, differentiation, apoptosis, and so on ^[1]. Cell proliferation is the cellular growth rate or as the quantified value for the daughter cell population. The process during which young, immature (unspecialized) cells turn into their mature (specialized) form and function is called cell differentiation. Apoptosis is the process of programmed cell death. In adults, apoptosis is used to get rid of the damaged cell from the body beyond repair ^[2]. As the first step towards improving human health, the source and isolation method of exosomes have to be reliable and efficient.

Pros of Exosomes for Therapeutic Delivery

• Biocompatibility and stability in body fluids

Exosomes are compatible with living tissue by assuring that the product poses minimal toxicity, injury potential or immunological activity. They can stay in the circulatory system for longer periods and are protected from degradation by extracellular proteases.

• Naturally derived low immunogenicity

Immunogenicity refers to the ability of a drug to induce an unwanted immune response. In some cases, immunogenicity is also defined as the strength or magnitude of an immune response. Exosomes are non-immunogenic in nature due to similar composition as body's own cells.

• Ability of guiding therapeutic cargo across blood brain barrier (BBB)

BBB is a selective barrier that functions to protect the brain by restricting the entry of potentially neurotoxic molecules ^[3]. However, approximately 98% of small molecules and almost all macromolecular drugs (e.g., nucleic acids, polypeptides, and proteins) are eliminated from the brain due to BBB. The high-density exosomes with a diameter smaller than 70nm are small enough to cross BBB and deliver drugs to the brain.

Exosomes Isolation

Various isolation techniques such as differential centrifugation, precipitation and ultrafiltration have been introduced to isolate high quality exosomes.

Differential centrifugation is the most common method of exosome isolation as it yields high purity exosomes. It consists of successive centrifugation steps with increasing centrifugation forces and durations.

Precipitation of exosomes is based on the aggregation of exosome in the presence of precipitating agents.

Ultrafiltration involves the procedure of filtering fluids through a filter with pores of a certain size. Exosome isolation protocols include several consecutive stages of filtration through filters, resulting in the gradual removal of particles larger than the pore size from the filtered fluid ^[4].

Below are the advantages and disadvantages of the three methods of exosome isolation.

Differential centrifugation
Advantages	Disadvantages
Fairly low cost Absence of additional chemical reagents	Relatively low yields of the exosome population [5]
Precipitation method
Advantages	Disadvantages
Exosomes of high morphological (structure) and functional quality	Low ‘purity’ of exosome preparation Contaminants like virus, bacteria and protein aggregates may remain
Ultrafiltration
Advantages	Disadvantages
Easy without special equipment	Loss of exosomes of small particle diameter [4]

 

A lack of standardization in exosome isolation methods leads to the development of various advanced techniques in order to optimize exosome isolation from a variety of biological fluids. Exosome isolation approaches will need further progress towards high purity and low operation time.

Exosome Therapy

Exosomes therapy is a new medical treatment that utilizes tiny vesicles called exosomes to deliver therapeutic molecules to specific cells in the body. These exosomes, which are naturally produced by stem cells, contain a variety of biomolecules including proteins, nucleic acids, and lipids that can be used to target specific cells and stimulate a desired response. Exosomes therapy has shown promise in a wide range of medical applications, including cancer treatment, tissue repair, and immune modulation. It is an exciting area of research that has the potential to revolutionize the way we approach many diseases and conditions.

 Benefits of exosome therapy

• Skin rejuvenation

As the largest organ in human body, skin acts as a protective barrier between the external and internal environment. As life progresses, physical changes in the skin are the first observation evidencing organismal aging. Skin aging is mostly due to the formation of reactive oxygen species (ROS) and shortening of telomere. Exosomes can contribute to multiple therapeutic effects including angiogenic ability, collagen synthesis and regulation of skin inflammation.

Exosomes promote vascularization as they strengthen the structure of skin vessels which are responsible for providing nutrient supply to the skin cells to maintain their activities. Collagen is essential for the elasticity of dermal layer. Exosomes help to increase collagen synthesis and prohibit the formation of collagenase that breaks down collagen. Exosomes were also shown to have therapeutic effect on atopic dermatitis (AD) as they inhibit local inflammatory reactions which can alleviate AD symptoms ^[6].

• Reduce inflammation

Exosomes function to relief the pathophysiological processes related to joints such as local inflammation, cartilage calcification and degradation of arthritic joints ^[7]. Thus, exosomes exhibit promising capability to regulate inflammatory response, promote angiogenesis to enhance blood flow and facilitate the repair of destroyed cartilage and subchondral bone. Exosomes derived from mesenchymal stem cells have been shown to relieve painful symptoms, with an analgesic action in several chronic pain models ^[8].

• Promote health in nervous system

 

Exosomes participate in intercellular communication, maintain the myelin sheath, and eliminate waste in the nervous system ^[9]. Due to their ability to penetrate the blood brain barrier, exosomes can protect disease-related molecules well, monitor disease development and enable early diagnosis. Exosomes have a high potential to help recovery of stroke as they are involved in increasing long-term neuroprotection after stroke, promoting nerve regeneration and enhancing neurological recovery. Exosomes can also minimize the risk of getting other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

Future

The exosomes field has made marvelous dives advancing in the past two decades. Whether exosomes can be used clinically as soon as possible depends largely on the results of optimization and improvement of the existing exosome problems. Having potential to maintain our overall health particularly in brain, joints and skin, exosome therapy may be the key to better function and quality of daily life. If you are interested in trying out exosome therapy in Malaysia, Luxxo Wellness has got you covered! Our high-quality exosomes are screened and manufactured in certified labs under highly standardized conditions, so you can be rest assured. The procedure will be aided by our Medical Director, nationally acclaimed geriatrician Dato Dr Rajbans Singh. Dr Rajbans will access your eligibility and personally attend to you to make sure you get the best care. Get in touch with us today at +6019 388 2775 to book an appointment or learn more about our exosome therapy.

 

References:

1. Ruivo et al. 2017. The biology of cancer exosomes: insights and new perspectives. Cancer Res.77, 6480-6488.
2. https://www.genome.gov/genetics-glossary/apoptosis#:~:text=Apoptosis%20is%20the%20process%20of,have%20been%20damaged%20beyond%20repair.
3. Saint-Pol et al. 2020. Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles. Cells, 9, 851.
4. Yakubovich et al. 2022. Principles and Problems of Exosome Isolation from Biological Fluids. Biochem (Mosc) Suppl Ser A Membr Cell Biol, 16(2), 115–126.
5. Livshits et al. 2015. Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Scientific Reports, 5, 17319.
6. Wang et al. 2020. Human mesenchymal stem cell-derived exosomes accelerate wound healing of mice eczema. Journal of Dermatological Treatment, 1-5.
7. Fan et al. 2022. Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment. Frontiers in Cell & Developmental Biology, 10, 949690.
8. D’Agnelli et al. 2020. Exosomes as a new pain biomarker opportunity. Molecular Pain, 16, 1744806920957800.
9. Liu et al. 2019. Role of Exosomes in Central Nervous System Diseases. Frontiers in Molecular Neuroscience, 12.