Medically reviewed by Robin Baradarian, MD, board certified physician, and Alfred Shirzadnia, DDS, cosmetic and implant dentist.
Exosomes have become one of the most talked-about topics in regenerative medicine and aesthetics, with more than 5,000 scientific papers now published on them each year.[1] But what are exosomes, exactly? Where do they come from, and how do scientists separate and measure particles far too small to see? A comprehensive 2023 review in Periodontology 2000 by Richard J. Miron and Yufeng Zhang answers these questions.[1] Here is a clear guide to what it covers.
What Are Exosomes?
Exosomes are the smallest type of extracellular vesicle (EV), the tiny membrane-wrapped packages that almost every cell in the body releases. They measure roughly 30 to 150 nanometers, about a thousand times thinner than a human hair, and they are found in most body fluids, including blood, saliva and urine.[1]
Think of exosomes as the body’s messaging system. Each one carries cargo from its parent cell, such as proteins, lipids and genetic messengers like microRNA, and delivers it to other cells. That cargo can change how the receiving cell behaves, influencing processes such as inflammation, immune responses and tissue repair.[1,2] Researchers have identified more than 8,000 proteins and nearly 200 lipids inside exosomes.[1]
How Exosomes Differ From Other Vesicles
Cells release three main types of extracellular vesicles, which differ in how they form and how big they are:[1]
| Type | Size | How it forms | Main role |
|---|---|---|---|
| Exosomes | 30–150 nm | Inside the cell, then released | Cell-to-cell communication |
| Microvesicles | 50–1,000 nm | Bud off the cell surface | Cell-to-cell communication |
| Apoptotic bodies | 500–2,000 nm | Released as a cell dies | Help clear dying cells |
A Brief History of Exosome Research
More than 50 years ago, researchers described tiny particles in blood plasma as “platelet dust.”[3] In 1983, two research groups tracking how maturing red blood cells shed unneeded proteins discovered that these cells released very small vesicles. These vesicles were later named exosomes.[4,5]
For years, exosomes were thought to be little more than cellular waste disposal. That view changed in 2007, when scientists showed that exosomes transfer genetic material between cells, revealing them as a genuine communication system.[6] Since then, interest has grown rapidly.
How Exosomes Are Made Inside Cells
Exosomes form through a three-step process inside the cell:[1]
- Uptake: the cell membrane folds inward, forming small compartments called endosomes.
- Packing: the endosome membrane buds inward again, creating many tiny vesicles inside a larger structure called a multivesicular body. Proteins, lipids and genetic material are loaded into these vesicles.
- Release: the multivesicular body fuses with the outer cell membrane and releases the tiny vesicles, now exosomes, into the surrounding fluid.
Once released, exosomes reach target cells by binding to receptors on their surface, transferring receptors, or fusing directly with the cell membrane to deliver their contents. Surface proteins help determine which cells an exosome targets.[1]
Where Do Therapeutic Exosomes Come From?
An exosome reflects the cell that made it, so its source matters. The review highlights several sources studied for regenerative uses:[1]
- Bone marrow stem cells: the most extensively studied, with research in liver, heart, brain and bone repair and in calming inflammation.
- Umbilical cord stem cells: studied in liver and kidney injury, fracture healing and gastrointestinal conditions.
- Adipose (fat tissue) stem cells: popular because they are relatively easy to obtain, and shown in studies to reduce inflammatory markers and support tissue recovery.
- Immune cells: exosomes from macrophages, dendritic cells and other immune cells can help regulate immune responses.
The authors stress that no single exosome source can regenerate every tissue, much as no single growth factor can. Matching the right source and preparation to each condition is an active area of research.[1]
How cells are grown also changes the exosomes they produce. Adjusting culture conditions, for example by adding certain signaling molecules or lowering oxygen levels, can alter both the number of exosomes released and what they carry.[1]
To see how exosomes are used in aesthetic and regenerative care, explore our PRF and exosome-enhanced regenerative therapies for skin, hair and joints.
How Scientists Isolate Exosomes
Body fluids and cell cultures contain a mix of exosomes, larger vesicles, proteins and cell debris, so isolating exosomes cleanly is a challenge. The review compares the main methods, each with trade-offs between purity, yield and cost:[1]
| Method | How it works | Strengths | Limitations |
|---|---|---|---|
| Ultracentrifugation | Spins samples at up to 100,000–150,000 times gravity to separate particles by density | Considered the gold standard; relatively inexpensive; handles large volumes | Time-consuming; lower yield; very high forces can damage exosomes |
| Size-exclusion chromatography | Passes the sample through a porous column that sorts particles by size | High purity; gentle on exosomes | Needs special columns; may carry over other particles |
| Ultrafiltration | Uses membranes with very small pores to filter by size | Simple; no special equipment | Filters can clog; smaller exosomes may be lost |
| Precipitation | Uses polymers to make exosomes clump and settle | Easy and economical; preserves exosome structure | Can leave behind contaminants |
| Immunoaffinity capture | Uses antibodies that bind proteins on the exosome surface | Very specific; can target exosome subtypes | Expensive; depends on antibody quality |
| Microfluidics | Uses tiny engineered channels to sort particles | Fast and precise, especially for diagnostics | Better suited to testing than producing treatments |
Ultracentrifugation is used in about 80% of studies.[1] In practice, laboratories often combine methods to balance purity and yield.
How Exosomes Are Counted and Characterized
Because exosomes are invisible under a regular microscope, specialized tools are needed to confirm what has been isolated and how much is there:[1]
- Nanoparticle tracking analysis (NTA): a laser lights up particles and a camera tracks their movement to calculate size and concentration. It does not alter the sample and is a preferred method for counting exosomes.
- Electron microscopy: the most common way to visually confirm exosome shape and purity, though it is time-consuming.
- Flow cytometry: widely available and able to analyze many features at once, though standard machines struggle with particles this small.
- Other methods: dynamic light scattering, tunable resistive pulse sensing and microfluidic devices also measure size and concentration.
Scientists also confirm exosome identity by checking for marker proteins on their surface, such as CD9, CD63 and CD81, and by analyzing their protein, lipid and genetic content.[1]
Exosomes vs. Stem Cells
Much of the regenerative activity of stem cells appears to come from what they release, including exosomes. The review outlines several reasons exosomes are attractive compared with whole-cell therapies:[1,7]
- Lower immune risk: exosomes are far less likely to trigger rejection, one of the main limits of stem cell therapy.
- No uncontrolled growth: exosomes cannot divide or copy themselves, avoiding concerns about cells multiplying unpredictably.
- Easier to store and use: they can be stored long term and are simpler to handle and apply than living cells.
- Small enough to travel: their tiny size lets them pass through barriers that cells cannot, and they avoid becoming trapped in the lungs as injected stem cells often do.
In animal studies of conditions such as kidney injury and liver fibrosis, exosomes performed as well as or better than the stem cells they came from.[1]
Quality, Storage and Standards
Because results vary widely with how exosomes are sourced, isolated and handled, the authors call for consistent standards. They recommend that researchers follow the International Society for Extracellular Vesicles’ MISEV guidelines and report their methods in full.[1,8,9]
Storage matters too. The society recommends keeping exosomes in a buffered saline solution at −80 °C; warmer storage reduces their number and content.[1,10]
For exosomes to become routine treatments, they must be manufactured under Good Manufacturing Practice (GMP) standards, with reliable cell banks, large-scale production methods and quality control testing.[1] The authors note that regulatory clearance is still developing, and many exosome products have not yet been cleared by the FDA or under the European CE system.[1] Choosing a provider who uses well-characterized, quality-controlled products is therefore important.
Key Takeaways
- Exosomes are tiny vesicles, 30 to 150 nanometers across, that cells use to send proteins, lipids and genetic messages to other cells.
- Their effects depend on the cell they come from, such as bone marrow, umbilical cord or adipose stem cells.
- Ultracentrifugation is the gold-standard isolation method, though several alternatives offer different trade-offs.
- Compared with stem cells, exosomes carry lower immune risk, cannot multiply and are easier to store and use.
- Standardized manufacturing and quality control remain key to bringing exosome therapies into everyday practice.
This article summarizes published research for educational purposes and is not medical advice.
About the Medical Reviewers
Robin Baradarian, MD, board certified physician.
Alfred Shirzadnia, DDS, graduated from NYU College of Dentistry and completed an oral and maxillofacial surgery fellowship at Wyckoff Heights Medical Center, where he also served as chief surgical resident. His work focuses on cosmetic dentistry, dental implants and full mouth rehabilitation, and he is a member of the American Academy of Cosmetic Dentistry and the American Academy of Facial Esthetics.
References
- Miron RJ, Zhang Y. Understanding Exosomes: Part 1—Characterization, Quantification and Isolation Techniques. Periodontol 2000. 2023;00:1–26. https://doi.org/10.1111/prd.12520
- Kalra H, Drummen GP, Mathivanan S. Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int J Mol Sci. 2016;17:170.
- Wolf P. The Nature and Significance of Platelet Products in Human Plasma. Br J Haematol. 1967;13:269–288.
- Harding C, Heuser J, Stahl P. Receptor-Mediated Endocytosis of Transferrin and Recycling of the Transferrin Receptor in Rat Reticulocytes. J Cell Biol. 1983;97:329–339.
- Pan BT, Johnstone RM. Fate of the Transferrin Receptor During Maturation of Sheep Reticulocytes in Vitro: Selective Externalization of the Receptor. Cell. 1983;33:967–978.
- Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-Mediated Transfer of mRNAs and microRNAs Is a Novel Mechanism of Genetic Exchange Between Cells. Nat Cell Biol. 2007;9:654–659.
- Mendt M, Rezvani K, Shpall E. Mesenchymal Stem Cell-Derived Exosomes for Clinical Use. Bone Marrow Transplant. 2019;54:789–792.
- Lötvall J, Hill AF, Hochberg F, et al. Minimal Experimental Requirements for Definition of Extracellular Vesicles and Their Functions: A Position Statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.
- Van Deun J, Mestdagh P, Agostinis P, et al. EV-TRACK: Transparent Reporting and Centralizing Knowledge in Extracellular Vesicle Research. Nat Methods. 2017;14:228–232.
- Witwer KW, Buzás EI, Bemis LT, et al. Standardization of Sample Collection, Isolation and Analysis Methods in Extracellular Vesicle Research. J Extracell Vesicles. 2013;2:20360.
