The Science of Regenerative Medicine and Exosomes

In today’s aesthetic world, the heat around exosomes is palpable. From medical dermatology to aesthetic medicine, exosome technology offers the potential to change our skincare practice. This newly developing asset in the regenerative aesthetics toolkit is starting to outshine the promise of stem cells. Decades of stem cell research has shown that it is a specific population of exosomes, not stem cells, that are the drivers of tissue regeneration and skin renewal. Yet, the promise of regenerative medicine is often alongside the hype. As medical professionals, it is our responsibility to distinguish between the hype and hope. This article reviews the key questions to ask exosome companies prior to welcoming their technology into your practice.

REGENERATIVE MEDICINE 101

Let us start with the lexicon. Regenerative medicine is at the forefront of disruptive innovation as a new and evolving field that harnesses the body’s natural healing mechanisms to restore form and function. The toolbox of regenerative aesthetics includes stem cells, platelet-rich plasma (PRP), growth factors, peptides, and exosomes. Stem cells are the building blocks of life with the ability to self-renew (create new stem cells) and differentiate (create mature cells). There are several types of stem cells, including mesenchymal stem cells from bone marrow, adipose tissue, or umbilical cord blood; induced pluripotent or bioengineered stem cells; and embryonic stem cells. There are currently no FDA-approved stem cell therapies for skin regeneration or hair restoration. Platelet-rich plasma or platelet-rich fibrin (PRF) is a concentrated blood product with a cocktail of growth factors that can promote regeneration. Its effects can widely vary. It is offered as an off-label application for aesthetic use.

WHAT’S NEW? EXOSOMES

The latest addition to the regenerative medicine toolbox is a cell-free option: exosomes or extracellular vesicles; they are the messengers that carry key signals in your body. Topical application of exosomes derived from validated sources may be used to enhance the appearance of radiant skin for aesthetic purposes. Exosomes can vary by the source; it can be derived from platelets, mesenchymal stem cells, or other body fluids—all written in a different molecular language.

Not all exosomes are the same. Extracellular vesicles or nano-carriers come in various sizes and types that contribute to its variability in cargo (what is inside the vesicles) and surface decorations (what is outside the vesicles). It is important to have the right extracellular vesicles for the job (exosomes), which carry the regenerative cargo. If exosomes can be considered a gift box that carry your birthday present, aesthetic providers need to ask key questions from exosome companies to ensure that the gift box is not damaged or empty. These question categories include exosome source, exosome isolation technique, exosome concentration, exosome purity, and exosome efficiency (Figure 1).

TOP 5 QUESTIONS TO ASK EXOSOME COMPANIES

• Exosome Source: Ask about the cell of origin for your exosomes. If the source is mesenchymal stem cells or blood-based products, then ask about the patient donors and how these donors were screened prior to collection. These products are typically derived from human tissues or blood. Mesenchymal stem cell-derived exosomes are often expanded outside the human body in cell culture for days or even weeks before isolating the exosome product. Ask about their cell culture expansion process, as exosome sources can change in cell culture during manufacturing.
• Exosome Isolation: Ask about how the exosomes are manufactured or isolated from the cell sources. Is this performed in adequate manufacturing facilities? How do they avoid contamination? If high-speed spinning is used for isolation, how do they ensure that the exosome outer shell remains protected?
• Exosome Concentration: Ask about the exosome concentration and how the number of exosomes per vial is determined. Based on isolation strategy and exosome source, some products require refrigeration versus room-temperature storage. How long is åthe exosome product stable after reconstitution?
• Exosome Purity: Ask about how the exosome company has validated the cargo within the exosomes. What is contained within the exosomes? Is the exosome quality and purity consistent from batch-to-batch?
• Exosome Efficiency: Ask about the effect of topical exosomes alone—without combination treatments such as microneedling or device-pairing. It may be prudent to request “before-and-after” photographs of the effects of an exosome product alone to review its singular potential.

Worth the Wait

Exosomes have several benefits for tissue regeneration including anti-oxidant and anti-inflammatory effects. They can be used for diagnostic and therapeutic purposes. For patients with chronic skin diseases, such as atopic dermatitis or eczema, there is potential for liquid biopsy and calculating patient-specific outcomes. Such medical indications require FDA approval through an investigational new drug (IND) application. Topical exosomes also have the potential to disrupt the aesthetics market. Yet use via injection into subcutaneous tissues or microneedling requires FDA approval. Targeted clinical trials with FDA IND could offer insight into their respective mechanisms of action for future use as a novel biostimulatory injectable.

In the aesthetic market where the fear of missing out on the latest technology can be a strong force, the pause for good science and validated technology is worth the wait.