EXOSOMES IN SKINCARE PART III – We Launched! What a Beautiful Sight.

What a liftoff!  Our name is in lights!

In March 2019 and in July 2021, BFT introduced its readers to the rapidly evolving science of exosomes and their potential for use in skin aesthetics. This post provides an update on exosome-based skincare products that are currently available while also announcing that the company founded by your humble hosts (Cellese, Inc. – producer of AnteAGE and AnteAGE MD brands) entered the fray by launching an exosome product at the July 2023 Aesthetics Show in Las Vegas. Saying we saw our name in lights is an understatement.

This photo was taken of our new exosome product being displayed on the world’s largest LED screen which covers the new Madison Square Garden Globe amphitheater in Las Vegas.

In this post, we discuss the available exosome products and what makes them different from one another. In the process, you will learn why we consider our newly launched product  “best in class”. After more than a decade in the market, and literally starting as three guys in a garage, Cellese products now enjoy an international reputation for efficacy, safety, and leading-edge  science. Our marketing messages, now in multiple languages, reflect our continued commitment to scientific integrity and forthright professional and consumer education.

Links to previous barefacedtruth.com exosome posts:

EXOSOMES -very small, very mighty, very important. March 2019

EXOSOMES IN SKINCARE – PART II  July 2021

Brief Review

Exosomes are miniscule nanoscale double-layered lipid “envelopes” secreted at the surface of nearly all cells. Exosomes contain cytokines, chemokines, DNA, RNA, miRNA and other proteins from the cells of origin to neighboring or distant receptor (“target”) cells, thereby altering target cell function.  Research has revealed that exosomes are exceedingly important in the cell-to-cell communication of all complex organisms including animals, plants and even fungi. No exosomes mean no complex multicellular life.

Exosomes originate within cells in multivesicular bodies (MVB),  which spill their exosomes into intercellular fluid when the MVB fuses with the cell membrane.

Interest in exosome research has grown exponentially over the past decade or so. In 2006, seventy-six articles about exosomes were published, according to PubMed.gov, the online world repository of peer-reviewed medical literature. That number increased to 271 in 2011, 1088 in 2016, and last year the number grew to 5203. The cumulative number to date is 28,663.

As one would expect, more research leads to more peer-reviewed articles being published, more protective patents being issued, and more public research dollars being expended. The graphs below illustrate the magnitude of these increases over the past two decades.

The goal of this activity, of course, is sufficient development to enable application of exosome science to improve the healthcare of humans and animals. Because they are naturally excreted by all cells into all bodily fluids, exosomes hold great promise as biomarkers for diagnosis of many diseases including cancers. The ability to modify their contents in the laboratory (called cargo), may lead to new drug and vaccine delivery methods. Administration of exosomes to patients appears feasible as a beneficial treatment for a variety conditions and diseases.

There is enormous global interest in this subject. ClinicalTrials.gov currently lists 328 trials exploring uses of exosomes in the clinical setting. Methods of exosome administration include intravenous, intramuscular, subcutaneous, intrathecal (into the spinal fluid), topical local spray, and nebulized inhalation.

Topical application of exosomes has been proven of value in numerous studies in facilitating the healing of burns, wounds and in providing antiaging benefits as illustrated below. Aside from these examples, use of exosomes has proven beneficial in promoting viability of surgical skin flaps, managing systemic lupus erythematosus (SLE), psoriasis, atopic dermatitis, and other indications.

Thakur A, Shah D, Rai D, Parra DC, Pathikonda S, Kurilova S, Cili A. Therapeutic Values of Exosomes in Cosmetics, Skin Care, Tissue Regeneration, and Dermatological Diseases. Cosmetics. 2023; 10(2):65. https://doi.org/10.3390/cosmetics10020065

Exosome Producers and Technology

The most notable differences among manufacturers are source of cells, methods of isolation and procurement, method of preservations, reconstitution requirements, dose of exosomes in each produced “unit”, indications for use, method of administration, storage recommendations and shelf life. In the list below, with the exception of ExCoBio (South Korea), exosomes are derived from stem cells sourced from bone marrow, placental, adipose, and umbilical cord tissue. ExCoBio also includes “stem cells” derived from Damsk and Portland rose plants.

For our take on plant based biosignals in human skincare, go to:

http://barefacedtruth.com/2011/12/08/botanical-stem-cells-in-skin-care/

http://barefacedtruth.com/2012/09/06/botanicals-in-skin-care-part-1-slather-on-your-vegetables-theyre-good-for-you/

Please note: Information on our newly launched product, AnteAGE MDX Exosome Solution, is available under Cellese, Inc. section below.

BENEV (Mission Viejo, CA)

• Majority ownership of BENEV recently acquired by ExCoBio of South Korea – announced July 12, 2023. (Particulars of ExCoBio discussed below.)
• Exosomes products derived from Adipose Stromal Cells (Adipose-derived stem cells) and also from Dansk and Portland rose callus stem cells (rationale for roses?)
• 2011 BFT post of botanical stem cells in skincare: http://barefacedtruth.com/2011/12/08/botanical-stem-cells-in-skin-care/
• In USA, adipose stem cells obtained from liposuction medical waste typically women in their early to mid 50’s (average age.)
• Product dose 2.5 to 5 billion exosomes.
• Lyophilized (freeze dried) product with diluent to produce 5 ml reconstituted.
• Shipped on ice and to be refrigerated until use.

https://www.benev.com/

Cellese, Inc. (Irvine, CA and producers of AnteAGE, AnteAGE MD, and AnteAGE MDX brands)

• Founded by physician scientists (DrJohn and DrGeorge, your hosts at BFT)
• Recognized stem cell experts and producers of high science “best in class” products.
• Eleven-year history as leading brand in human stem cell derived cytokines and growth factors in skincare for home, professional and intra and post-procedure use.
• Globally recognized experts in culture and use of human mesenchymal stem cells conditioned media in skincare, hair retention and regrowth, and women’s intimate health.
• Exosome product is derived from co-culture of umbilical cord and bone marrow mesenchymal stem cells which provide exosomes with potent growth and regeneration biosignals in combination with robust anti-inflammatory activity. (See selected references below at end of this Cellese, Inc. section)
• Cellese products enjoy extraordinary history of safety and efficacy for over a decade.
• Available and used in thousands of aesthetic and medical practices worldwide.
• Millions of units sold and hundreds of thousands of users – North America, Latin America, Europe, Middle East, SE Asia, Australia

https://anteage.com/

To learn more about Cellese’s exosome science and enjoy a short lab tour at our Irvine, CA facility, click here.

For an AnteAGE MD brand overview, click here.

Select References with Abstract Excerpts:

Liu SJ et al. Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorate HaCaT Cell Photo-Aging. Rejuvenation Res. 2021 Aug;24(4):283-293. doi: 10.1089/rej.2020.2313. Epub 2021 May 6. PMID: 33607932.

“Umbilical cord mesenchymal stem cells (UCMSCs) have been identified as a potentially ideal cell type for use in regenerative therapeutic contexts owing to their excellent paracrine secretory abilities and other desirable properties. Previous work has shown that stem cell-derived exosomes can effectively reduce skin aging, but few studies have specifically focused on the role of UCMSC-derived exosomes in this context. [….] We found that UCMSC-derived exosomes were able to enhance normal HaCaT cell proliferation and migration while also inhibiting UVB-induced damage to these cells. These exosomes also reduced HaCaT cell apoptosis and senescence, increasing collagen type I expression and reducing matrix metalloproteinase (MMP1) expression in photo-aged HaCaT cells. Together, these findings indicate that UCMSC-derived exosomes have the potential to be used therapeutically to suppress skin aging.”

Kim YJ et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem Biophys Res Commun. 2017 Nov 18;493(2):1102-1108. doi: 10.1016/j.bbrc.2017.09.056. Epub 2017 Sep 14. PMID: 28919421.

“Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) play an important role in cutaneous wound healing, and recent studies suggested that MSC-derived exosomes activate several signaling pathways, which are conducive in wound healing and cell growth. In this study, we investigated the roles of exosomes that are derived from USC-CM (USC-CM Exos) in cutaneous collagen synthesis and permeation. We found that USC-CM has various growth factors associated with skin rejuvenation. [….] increased expressions of Collagen I and Elastin were found after 3 days of treatment on human skin. The results showed that USC-CM Exos is absorbed into human skin, it promotes Collagen I and Elastin synthesis in the skin, which are essential to skin rejuvenation and shows the potential of USC-CM integration with the cosmetics or therapeutics.”

Roşca AM, Ţuţuianu R, Titorencu ID. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Rom J Morphol Embryol. 2018;59(3):655-662. PMID: 30534802.

“…healing of chronic wounds is still a major cause of discomfort for the patients and a financial burden for the care system. [….] It has been shown that mesenchymal stem cells (MSCs) are able to improve the wound healing process by secreting factors with anti-inflammatory, anti-fibrotic and pro-angiogenic activities either as soluble molecules (growth factors, cytokines) or encapsulated within membrane vesicles (microparticles, exosomes). It has been shown that exosomes, the small membrane vesicles originating from the endocytic pathway, are the main mediators of MSCs paracrine effect. Their complex cargo (mRNA, microRNA and various anti-apoptotic and pro-angiogenic factors) has been found to induce migration and proliferation of fibroblasts as well as collagen synthesis [….]”

Wang ZG et al. Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells. Stem Cell Res Ther. 2020 Nov 27;11(1):511. doi: 10.1186/s13287-020-02032-8. PMID: 33246507; PMCID: PMC7694919.

DermaFirm* (South Korea and USA subsidiary, West Springfield, MA)

• IOHO, this company may be the example par excellence of using the buzz word of the moment for deceptive marketing.
• Website list numerous “exosome” products including: Hydra Exosome Cream, Hydra Exosome Lotion, Hydra Exosome Toner, Melavita-C Exosome Lotion, Elysee Exosome Ampoule, Exosome Ampoule Cera-HA, Hydra Exosome Cleanser, Purifying AC Exosome Cleanser.
• In examining the ingredient decks for these products, exosomes, even conditioned media seems to be missing in all formulations (If you care to, please re-check our work and see if you agree.)
• Their website discussed the benefits of umbilical cord blood stem cells then goes on to state: “…how can you incorporate these powerful stem cells and growth factors into your skincare routine? One option is to use products that contain salmon DNA extract (PDRN), which is derived from salmon roe and is rich in nucleotides that can help to repair damaged skin cells and promote cellular growth.” (Huh? Salmon roe = umbilical cord blood stem cells?)
• *We say poppycock to DermaFirm’s extravagant and near ubiquitous use of the word “exosome” and invite company personnel to correct us so we may become better informed.
• Remember Caveat Emptor, the Latin phrase that translates to “let the buyer beware”.

https://dermafirmusa.com/

Direct Biologics (Austin, TX)

• Investigational product using intravenous infusion of bone marrow MSC exosomes as treatment for COVID-19 acute respiratory distress syndrome (ARDS).
• BM-MSC selected as cell of choice due to abundant (63,000) published studies demonstrating potent anti-inflammatory and pro-healing secretome profile.
• Delivering 10 billion exosomes per milliliter of product.
• Delivered frozen and stored in ultra-low temperature freezer (up to -80 °C for 5 yrs)

https://directbiologics.com/

Dp Derm (North Miami, FL)

• MG-EXO-SKIN DP Dermaceuticals Serum for microneedling contains: “exosomes derived from mesenchymal stem cells, Hylafuse, calphasomes, Vit C, Zinc, Pro-vitamin B5, and aloe vera.”
• No information about exosome concentration, mode of isolation, need for freezer or refrigeration or lyophilization. On-line information tends to imply “room termperature” is not problematic due to lack of information to the contrary.
• EXO-SKIN^TM Exosome Therapy serum comes in one-ounce airless pump for daily use. Full ingredient deck was not available through multiple Google searches making it exceedingly difficult to consider this a true exosome product. An emulsified product with many blended ingredients would obliterate any exosomes.
• BFT strongly doubts formulation and storage parameters of any Dp Derm products enable preservation of intact exosomes in final products. Not convinced these are true exosome products.

https://dpderm.com/

ExCoBio (South Korea)

• Exosomes produced from adipose-derived stem cells for the global market (secretome of adipose-derived stem cells has been demonstrated to be tilted toward pro-inflammation.)
• Some products contain exosomes derived from Dansk and Portland roses. (Really?)
• 2011 BFT post of botanical stem cells in skincare: http://barefacedtruth.com/2011/12/08/botanical-stem-cells-in-skin-care/
• Product dose 2.5 to 5 billion exosomes.
• Lyophilized (freeze dried) product with diluent to produce 5 ml when reconstituted.
• Shipped on ice and to be refrigerated until use.

http://www.exocobio.com/bizdemo87737/eng/index.php

Elevai (Newport Beach, CA)

• Human umbilical mesenchymal stem cell conditioned media plus dozens of other ingredients. Conditioned media contains exosomes and other biosignals/proteins.
• Website discusses exosomes but products are NOT concentrated exosomes at all.
• Intact exosomes are impossible in an emulsified, room temperature product with many other ingredients. Indicated for “post-procedure” use.
• IOHO, marketing is highly deceiving and sadly, too typical of the skincare industry.
• BFT post about dubious marketing in the skincare industry: http://barefacedtruth.com/2019/08/14/fool-me-once-shame-on-you-fool-me-twice-shame-on-me/

https://elevaiskincare.com/exocel

Exocel Bio (San Diego, CA)

• Exosomes derived from stem cells sourced from the chorion layer of the placenta.
• Ultrafiltration and flowcytometry used to concentrate exosomes.
• Storage and shipment in frozen state -20 °C to -80 °C.
• Products for skin, hair, and veterinary (horse, dog, cat) indications.
• Concentration by ultrafiltration using 22 µm pore size.
• Depending on indication, dose varies from 5 B to 25 B for skin, 100 B for hair
• Expensive

https://www.exocelbio.com/

Kimera Labs (Miramar, FL)

• “Optimal-Purity Exosomes for Clinical Research”
• Exosomes derived from perinatal mesenchymal stem cells, specifically the chorionic plate of the human placenta.
• Received FDA investigational new drug clearance for human trials using intravenous injection of exosomes to treat COVID-19 adult respiratory distress syndrome (ARDS).
• Focused on pharmaceutical grade MSC exosomes for diagnostic and therapeutic applications.
• Product for healing of bone and tendon wounds in animals.

https://kimeralabs.com/

Regan Suppliers (Scottsdale, AZ)

• Supplier of PRP kits, cryo containers, umbilical cord tissue allographs, ultrasound machines, suture training kits and more.
• ReBellaXO branded exosomes produced by another vendor but marketed by Regan Suppliers.
• Exosomes sourced from umbilical cord and Wharton’s Jelly stem cell cultures.
• 15 billion exosomes per cc.

https://www.regensuppliers.com

RION (plated) (Rochester, MN)

• “…developing room temperature stable exosome therapeutics”
• “Purified Exosome Product” derived from platelet exosomes.
• Nowhere on website is there language about exosome harvesting or concentration. We are more likely dealing with “activated” or lysed platelets which spill all contents including exosomes. (Company spokesperson: please correct us if you wish, and can.)
• Platelets naturally have a highly inflammatory secretome and are pro-thrombogenic.
• Daily use and post-procedure products available.
• Company website has pipeline with products for “wound healing, acute myocardial infarction (ischemic heart attack), female stress urinary incontinence, and musculoskeletal” indications.

https://riontx.com/