In a piece published in the Dermatology Times, Zoe Draelos, M.D. misinforms the dermatological community about exosomes.

Exosomes are an exciting technology, and the complications of this technology are many. I’ve been publishing about exosomes for many years, and if you’d like to read a deep dive into exosomes, you can read my free Elsevier-published review chapter on exosomes that I wrote back in 2016. Named, “Exosomes: smart nanospheres for drug delivery naturally produced by stem cells,” the chapter is available free on Research Gate. You can also read my recent blog on exosomes, and in another blog read about some of the companies bringing sub-optimal exosomes to the market. As I described in my 2013 paper, “Stem Cell Therapy Without the Cells,” using a reductionist strategy where only some of the molecules are used, instead of all the molecules, is a suboptimal strategy. Using only exosomes is reductionistic and suboptimal. My blog, chapter, and papers, explains what Zoe Draelos doesn’t understand about exosomes. Use the secretome (all of which is released by the cell), not just the exosomes. A number of studies have found that exosomes don’t have the same efficacy as does the complete secretome (the natural secretome that contains both the exosome faction and the soluble fraction), including for actions such as immune modulation and regenerative capacity.

I’ll keep it simple here in this blog, and refer to one part of the article by Zoe Draelos. I’ll focus on the following paragraph from her article: “Exosomes for aesthetic use are derived from adult or mesenchymal stem cells. These cells can be harvested from umbilical cord mesenchymal stem cells or adipose-derived stem cells. The exosomes are isolated by differential centrifugation from culture media. The culture media is first centrifuged to remove higher mass contaminants. The centrifugation then occurs at higher and higher speeds until the exosomes aggregate as a pellet in the bottom of the centrifugation tube. These purified exosomes can then be placed into cosmetic formulations.”

While some companies do use damaging techniques to process exosomes, for example ultracentrifugation of the cellular culture media to isolate exosomes, and then lyophilization (freeze-drying) the exosomes to preserve them, some companies, such as my own, Neogenesis Inc, use fresh exosomes that haven’t been damaged by ultracentrifugation and lyophilization processes. Ultracentrifugation and lyophilization are used for the convenience of the companies, allowing the exosomes to be easily stored and easily shipped as a small dehydrated, frozen pellet. Scientists have been isolating exosomes for years. The process is challenging. To better understand exosomes, scientists need to isolate them, but they’re hard to isolate because other molecules, particularly proteins not in the exosome, co-isolate with the exosomes. And the processes used for isolation are damaging. For therapeutic purposes, isolation of exosomes is unwarranted – if you want an optimal product.

Isolation of exosomes is unwarranted for three major reasons: 1. as I discussed, the process damages exosomes rendering damaged proteins on the inside of the exosome as well as those tethered to the outside, and 2. the highly functional proteins and polysaccharides attached to the outside of the exosome can by stripped away – the exosome is denuded, and 3. cells release many beneficial molecules that are not contained in or on the exosomes. When cells release molecules, there is an exosomal fraction and a soluble fraction. The two fractions work together synergistically, and excluding one or the other yields a suboptimal product. In other words, using just the exosomes instead of the exosomes plus the soluble fraction (the molecules secreted by the cell but not contained in the exosomes) yields a suboptimal product.

Exosomal cargo is protected from enzymatic, pH, and heat degradation given its encapsulation within the lipid bilayer of exosomes. Exosomal proteins have been found to maintain their native conformation and functionality for long periods of time, where, for example, exosomal phosphoproteins were stable over a storage period of at least 5 years (Chen et al, 2017). Exosome contain heat shock proteins, for example, that repair proteins and may finish the folding of proteins within the exosome (Maguire, 2016).

Exosomes are complicated and we still have much to learn. But what we have learned is that fresh, unprocessed exosomes work best because they’re undamaged, and when the exosomal molecules are combined with the other molecules that are released by the cell but not contained in the exosomes, we have an optimized therapeutic. The unprocessed exosomal fraction in combination with the unprocessed soluble fraction works best.