Tag Archives: neogenesis

NeoGenesis’ New Topical Probiotic Products, MB-2 and MB-3, Feature 5 Strains of Live, Colonizing Symbiotic Bacteria

Based on many recent scientific studies of using live, symbiotic bacteria in a topical application, NeoGenesis has launched a new probiotic, topical skin care product (MB-2) and will be launching MB-3 soon. I briefly explain some of the science for using topical probiotic products in this post.

I’ve been publishing about (Maguire and Maguire, 2017) and developing topical probiotic products (MB-1 was launched in 2015) for well over a decade. The data for topical symbiotic bacteria colonizing and benefiting the skin are rapidly accumulating. For example, topically applied Lactobacilli have been found to temporarily colonize the skin and to directly compete with skin pathogens through adhesion inhibition, production of antimicrobial metabolites, and by influencing pathogen metabolism. The competitive anti-pathogenic action of Lactobacilli has been described mechanistically for common skin pathogens, such as Staphylococcus aureus, Cutibacterium acnes, and Candida albicans (DeLanghe et al, 2021). Recently, studies of live Lactobacillus crispatus (LBC) demonstrated benefit to the skin when compared to inactivated LBC biomass, stimulating collagen in vitro. Moreover, the live LBC was stable in formulations not containing antimicrobial preservatives and was found to improve dermis density and wrinkle appearance in vivo.

Microbes and human cells have co-evolved for billions of years, through which they have been exposed to many types of molecules produced by each other and acting in bidirectional signaling pathways (Wu et al, 2025). For example, Lactobacilli have an immunomodulatory capacity associated with a reduction in excessive skin inflammation (Delanghe et al, 2021). Their influence on the immune system is mediated by bacterial metabolites and cell wall-associated or excreted microbe-associated molecular patterns (MAMPs). Lactobacilli acting as immune modulators associated with a reduction in excessive skin inflammation exert their influence on the immune system by secreting many bacterial metabolites, a type of postbiotic (this is a term I introduced in 2019; Maguire and Maguire, 2019), along with the cell wall-associated MAMPs that are not released but integrated into the cell of the bacterium. In addition, Lactobacilli can also enhance the skin barrier function, which is often disrupted as a result of infection, trauma, or in inflammatory skin diseases such as eczema and psoriasis. Lebeer et al (2022) found that the Lactobacillis species L. crispatus, L. iners, L. gasseri, and L. jensenii, all still belonging to the genus Lactobacillus strictu sensu, have a broader human adaptation to stratified epithelium than merely the human vaginal epithelial cells, based on their association with healthy skin. In other words, Lactobacilli colonize the skin just as they do in other epithelial tissues. However, these colonies of bacteria on the skin can be disrupted by a number of extrinsic and intrinsic factors, such as harsh chemicals and aging. For example, aged skin contains significantly fewer L. crispatus (a beneficial symbiont) than young skin. Let’s now breiefly look at how symbiotic bacteria benefit the skin through quorum sensing and the release of post-biotic molecules, including molecules that will inhibit pathogenic bacteria such as certain strains of Staphlacoccus aureus.

Quorum Sensing and Post-Biotic Release

Mechanisms of quorum sensing is different for gram-positive versus gram-negative bacteria. Regardless, quorum sensing molecules (AIP or QS molecules) can work within species or on other species to control growth. This is an important means by which symbiotic bacteria, such as B. subtilis, can inhibit pathogenic bacteria such as S. aureus.

As bacteria grow, they secrete and sense signaling molecule in the surrounding environment. By detecting variations in the concentration of these signal molecules, bacteria can modulate the expression of related genes, thereby regulating associated behaviors. Consequently, interfering in bacterial QS signaling to either promote or inhibit the development of lactic acid bacteria (LAB) biofilms holds substantial significance in terms of enhancing skin immunity, promoting skin health.

Quorum sensing allows bacteria to communicate and coordinate collective behaviors by sensing population density through chemical signals, or autoinducers. While primarily species-specific, interspecies communication also occurs when different bacteria produce or detect shared autoinducers like autoinducer-2 (AI-2), a “universal” signal molecule used by many species. This interspecies communication can lead to either cooperation or competition, influencing functions such as biofilm formation, virulence, and resistance against other microbes.

For example, colonization of the skin by Staphylococcus aureus is associated with exacerbation of atopic dermatitis (AD). Proteases and phenol-soluble modulin α (PSMα) secreted by S. aureus leads to endogenous epidermal proteolysis and skin barrier damage that promotes inflammation (Williams et al, 2019). Other species of bacteria residing on normal skin can produce autoinducing peptides that inhibit the S. aureus agr system, in turn decreasing PSMα expression. A number of bacteria types, such as Bacillus subtilis (it secretes lactic acid), can quorum sense (Spacacan et al, 2020) and react to the S. aureus overcolonization by inhibiting the S. aureus through disruption of their QS system (Leistikow et al, 2024).

Quorum-sensing systems in the skin can be divided into two paradigmatic classes: LuxI/LuxR–type quorum-sensing systems in Gram-negative bacteria and oligopeptide/two-component–type quorum-sensing circuits in Gram-positive bacteria. All of this is very complicated, relaizing that bacteria have elaborate chemical signaling systems that enable them to communicate within and between species is only recently been explored and the field is emerging quickly. Based on our current knowledge, I’ve developed two new products, MB-2 and MB-3, using symbiotic, live bacteria known to perform QS or interfere with QS in other bacteria strains and promote skin benefits, including reduced inflammation and barrier function rebuild.

Interspecies Quorum Sensing Fosters Both Competition and Collaboration

To be clear, quorum sensing between different bacterial species occurs as well. For example, some species cannot produce their own autoinducers, but have receptors for the autoinducer molecules of other species, allowing them to sense and respond to others in their environment. Like human behavior, bacteria behavior operates on a continuum of individualism and collectivism. This quality can breed conflict, but also collaboration and interspecies quorum sensing can take both forms. In other words, the good guys, the symbiotic bacteria, can work together through quorum sensing among themselves (intraspecies quorum sensing) to inhibit the bad guys, the pathogenic bacteria, through interspecies quorum sensing. The good guys can be fighting some bacterial species, such as S. aureus, that use quorum sensing to enhance each other’s virulence.

Let’s now look at the five symbiotic bacteria that are contained in MB-2 and MB-3

Lactobacillus plantarum

Lactobacillus plantarum treatment reduced wound bacterial load, neutrophils, apoptotic and necrotic cells, modified IL-8 production and induced wound healing (Peral et al, 2010). When topically applied to a disease skin model for acne, L. plantarum induced a significant reduction in viability of virulent bacteria phylotypes, lipid production, and modulated inflammatory markers (Podrini et al, 2023).  Further, L. plantarum whole cultures promote tissue repair, and this bacterium may also improve the healing of diabetic wounds in rats through the regulation of inflammatory cytokines (Ishi et al, 2023). In a study of 23 subjects, topical L. plantarum in a cream formulation was found to benefit skin aging properties, including TEWL, barrier function, and wrinkles (Elvebakken et al, 2023).

 Lactobacillus crispatus

An oily suspension containing Lactobacillus crispatus and Lacticaseibacillus paracasei was found to benefit Seborrheic dermatitis (Truglio et al, 2024). In a study of 29 women with topical application of L. crispatus, the density of the sub-epidermal zone significantly increased vs baseline by 11% and of the dermis by 6% (+5% vs placebo). As I mentioned in the introduction,, studies of live Lactobacillus crispatus (LBC) demonstrated benefit to the skin when compared to inactivated LBC biomass, stimulating collagen in vitro. Moreover, the live LBC was stable in formulations not containing antimicrobial preservatives and was found to improve dermis density and wrinkle appearance in vivo.

Bacillus subtilis

Topical application of live Bacillus subtilis has been found to reduce the number of pathogenic bacteria in skin, including S. aureus (Moskovicz et al, 2021; Piewngam et al, 2023). Topical application also helps to reduce acne breakouts (Ma’or et al, 2023). B. subtilis is being developed for drug delivery for a number of reasons (Montgomery et al, 2024). It may have advantages over other candidate bacteria as a platform for drug delivery to the skin because of its safety profile and genetic tractability. It is found in the skin microflora and is metabolically active on the skin. It is nonpathogenic and has natural antimicrobial properties against pathogenic staphylococci and fungi. B. subtilis has generally regarded as safe status from the FDA, and multiple B. subtilis probiotic products as well as a genetically modified strain of B. subtilis are currently commercially available. Further, an important characteristic of B. subtilis is that it is commonly used in biotechnology for the production of proteins, vitamins, and antibiotics because of its efficient protein secretion system, and ease of cultivation, factors that mean it can work well when topically applied to the skin as a probiotic.

Bacillus coagulans

LactoSporin, a metabolite of Bacillus coagulens, cream topically applied for 10 weeks resulted in a significant reduction in visibility of wrinkles around crow’s feet, nasolabial folds, frown lines, and facial fine lines compared to baseline and placebo by dermatological and Antera imaging assessments (Majeed et al, 2023). . Optimal conditions for growth include a temperature range of 30–50°C and a pH level of 5.5–6.5, matching the surface of the skin. This bacterium exhibits weak adhesion to epithelial cells, which prevents long-term colonization, but allows temporary colonization and yielding positive effects.

Lactoccus lactis

Various strains of L. lactis have recently been reported to induce anti-inflammatory activity in vitro (Luerce et al, 2014). Administration of L. lactis LB 1022 improved clinical AD symptoms, decreased serum IgE and suppressed the Th2 cytokines secretion, such as IL4, IL-13, and TSLP in blood, which are factors found to be elevated by AD. Similarily, oral L. lactis LB 1022 may have a protective effect against AD by reducing high IgE serum levels and Th2-related responses that arise from an imbalance in the gut microbiota. Topical application of L. lactis is likely to have similar effects on AD, but given the likely lower colonization levels when topically applied, requires more frequent dosing to achieve similar positive results. It is also possible that L. lactis ferments glycans on the surface of the skin, thus producing beneficial lactic acid that may then be fermented into beneficial short chain fatty acids which then regulate the immune system and reduce inflammation.

Summary

As you can read here in the studies I’ve mentioned, there is much accumulating evidence for the benefits of the 5 types of symbiotic bacteria that I’ve chosen to include in our NeoGenesis MB-2 and MB-3 products. Working with a number of dermatologists in the USA, we’ve had remarkable postive results in compromised, inflammatory skin conditions where MB-2 (bacteria in an occlusive base) serves those conditions with interupted barrier function, such as atopic dermatitis and MB-3 (in a non-occlusive oil base) serves those conditions with a more intact barrier and oily and pustule-prone skin.

Skin Pores – Reducing Their Size

Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, ageing, diet, chronic ultraviolet light exposure, comedogenic xenobiotics, acne, genetic and epigenetic predisposition, and seborrhoea. Most of these causative factors of enlarged pores, being exogenous and controlled by enironmental factors, means you can do something about it. There are procedures and topical products you can use to reduce pore size.

From: Yousef et al (2024)

Although the pathogenesis of enlarged facial pores is still not fully understood, three factors are thought to be key to the pathology: 1) high sebum production, 2) decreased skin elasticity around pores, and 3) increased hair follicle volume. Other factors, including chronic recurrent acne, diet, sex hormones, and skin care regimens, such as inappropriate use of cosmetics, modern Western diets, washing habits, and sun exposure, also affect pore enlargement. Many of these factors will affect the epigenetics of the skin and therefore the skin’s health and potentially pore size. Epigenetics are regulated by your environment, so there is much you can do to reduce enlarged pores.

Causes of Large Pore Size

In cross-sectioned images of conspicuous, enlarged pores, a strongly undulated epidermal–dermal junction was commonly observed around a pore’s opening. Areas with this feature correlated well to the areas with larger hollows and an uneven skin tone. (Sugata et al, 2007).

Recent clinical studies have confirmed the cause of facial pore size to be multifactorial. A positive correlation of pore size and number with sebum output level has been confirmed by several studies (Roh et al, 2006; Kim et al, 2013). Enlarged pores increase with age, up to 40 years, and then stabilize or only slightly increase (Jung et al, 2018). Another significant correlation was detected between skin elasticity and pore number in two independent studies suggesting that the structure of dermis could be involved in pore widening (Kim et al, 2013; Hameed et al, 2019). Other observations found pore counts were related to wrinkle severity; and the loss of Microfibril-associated glycoprotein-1 in the hair follicle/pore area with aging and photo-exposure, indicating a lack of matrix support in the dermis (Zheng et al, 2013; Jung et al, 2018).

Both epidermal and dermal structual impairments have been identified as a cause of large pores. Microscopic imaging of pores revealed inner structural changes affecting skin, including a lower density of collagen in the deeper dermis, a thicker stroma and coarser collagen fibers forming a tubular structure around the follicle, and an irregular basement membrane ultrastructure, all of which may result in an altered distribution of skin tensions (Sugata et al, 2008;  Sugiyama-Nakagiri et al, 2008; Mizukoshi and Takahashi, 2014). These ultrastructural alterations may result from inflammation, and recent data suggest inflammaging, mediated by complement activation (immune system proteins), as one of the possible inflammatory agents in the formation of enlarged facial pores (Qiu et al, 2024). Bacteria, such as Staphlacoccus aureus, infect hair follicles and pores, and the question remains, does the inflammation with this sort of infection enlarge the pore. Defects in epidermal morphology around pores have also been discovered, such as epidermis thickening and acanthosis (thickening of the stratum spinosum layer), likely indicating abnormal and possibly excessive keratinocyte proliferation ( Mizukoshi and Takahashi, 2014).

Procedures to Reuce Pore Size

Procedures, such as Micro-focused ultrasound with visualization (MFU-V), have been found to reduce pore size. MFU-V uses focused ultrasound energy to lift and tighten the skin by delivering heat to specific tissue layers beneath the skin’s surface, stimulating collagen production and causing skin tightening according to The Journal of Clinical and Aesthetic Dermatology. The visualization aspect of the procedure allows practitioners to see the underlying tissue during treatment, ensuring precise targeting and optimal results.

Topical S2RM to Reduce Pore Size – It’s Not Just the Exosome, It’s the Secretome

But are procedures needed to reduce pore size? No, the right choice of topical skin care products can significantly reduce pore size too. The secretome from adipose mesenchymal stem cells, something used in the NeoGenesis S2RM technology, significantly reduces pore size. That inflammation inducing the ultrastructual changes causing pores to enlarge can be reduced- reduce the inflammation with ADSC secretome found in the NeoGenesis S2RM technology. Remember, It’s Not Just the Exosome, It’s the Secretome that is optimal for reducing inflammation and regenerating tissue – including the tissue that constructs the pore. Changes of TEWL found that ADSC secretome can faciltate the recovery of the skin barrier function (Zhou et al, 2013), which can be explained by ADSC secretome normalizing the proliferation and migration of human primary keratinocytes as reported by Moon et al (2012). Both the epidermis (Ren et al, 2024) and dermis (Silveira et al, 2022) and hypodermis (An et al, 2021) are regenerated by ADSC secretome, with ADSC secretome containing collagen type IV needed to build the basment membrane, thereby regulating that “undulated epidermal–dermal junction” found to underly increased pore size.

I want to emphasie that inflammaging, inflammation that occurs as we age, is exposome induced. Those who eat well and live in an healthy envionment don’t suffer from inflammaging (Franck et al, 2025). As Franck et al write, “Inflammaging, as measured in this manner in these cohorts, thus appears to be largely a byproduct of industrialized lifestyles, with major variation across environments and populations.” In other words, if you live a healthy lifestyle, chronic inflammation, including inflammaging, is something you won’t suffer. This will reflect in your skin health, and your skin’s pore size.

Summary

Pore size in the skin depends on your envionment, your so-called exposome. Healthy skin is beautiful skin, including beautiful, healthy pores. Eat well to keep the skin healthy with sebum production levels normal and therefore reducing a risk factor for increased pore size. And the right choice of topical skin care products can help keep the skin healthy and pore size normal.

Why NeoGenesis Uses Sodium Benzoate and Gluconolactone As An Antimicrobial Preservative System

The use of gluconolactone and sodium benzoate together as a preservative system has, 1.  a wide range of global regulatory acceptance, 2. Broad spectrum antimicrobial activity, 3.  ECOCERT/COSMOS-accepted. 4.NATRUE- approved and Soil Association-approved, 5. added moisturization benefit, and 6. anti-inflammatory properties. This safe and efficacious preservative system with skin benefits compares to others such as phenoxyethanol that is toxic and easily penetrates the skin into the blood.

Sodium Benzoate

Cinnamon contains a major compound, cinnamaldehyde, which is converted into cinnamic acid by oxidation. In the liver, this cinnamic acid is β-oxidized to benzoate (Abd El-Mawla et al., 2001) that exists as sodium salt (NaB) or benzoyl-CoA. As a safe metabolite of cinnamon, sodium benzoate (NaB), is a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, found to increase the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS (Jana et al, 2013). So safe is NaB that it is approved as an injectable for certain brain diseases (Misel et al, 2013).

NaB is of medical importance as it is a component of Ucephan, a FDA-approved drug used in the treatment for hepatic metabolic defects associated with hyperammonemia such as urea cycle disorder in children (Leonard and Morris, 2002; Scaglia et al., 2004). It is also widely used as a preservative in broad range of foods and cosmetic products (Nair, 2001). It is non-toxic and can be administered as a solution in drinking water. One study reported that a 2% solution of NaB in drinking water is safe for lifelong treatment in mice without any measurable negative side effects (Toth, 1984). Recent studies have found that NaB is capable of modulating both innate and adaptive immune responses (Brahmachari and Pahan, 2007; Brahmachari et al., 2009; Brahmachari and Pahan, 2010), several studies finding that NaB in switching the balance of Th cell subsets toward anti-inflammatory Th2 and Tregs types (Brahmachari et al, 2007; Rezaei et al, 2016). Inflammatory cytokines found in arthritis were also found to be decreased with NaB using in vitro models (Bemani et al, 2020).

NaB is not only efficacious as an antimicrobial preservative and as an immune modulator, but it is also safe – it does not convert to benzene under the conditions of use as a cosmetic or food preservative as told by some ignorent people I’ve heard talk about the subject. This was a concern back in the 1990s, but was cleared as a problem in the 2000s. Those initial reports from the FDA that small amounts of benzene were in soda drinks has now been found to be in error, as the FDA has said, “the TDS [FDA’s Total Diet Study lab] benzene results appeared to be unreliable.” Benzene formation in the analytic techniques used by the FDA’s TDS lab in Kansas were the culprit, along with contamination (FDA Report, 02/25/2022).

Gluconolactone

In nature, GLA can be found in honey, tofu, cheese, wine, bread, fruit juices, among others, and as an approved food additive

Gluconolactone (GDL) is anti-inflammatory by enhancing in vitro induced (i)Treg differentiation and function, and in imiquimod-induced autoimmunity in mice, treatment with GDL alleviates inflammation by inhibiting TH17 cells (Li et al, 2025).

In patients suffering from cutaneous lupus erythematosus, topical application of a GDL-containing cream controlled skin inflammation and improved the clinical and histologic appearance of the skin lesions within 2 weeks (Li et al, 2025).

GLA exhibits antioxidant and moisturizing effects. It protects elastin fibers from UV-induced degradation (Jarząbek-Perz et al, 2023).

NaB and GLA Compared to Phenoxyethanol

Compared to anti-inflammatory and non-toxic NaB and GLA, phenoxyethanol (PE) is known to be toxic to epithelial cells (Wang et al, 2020). At concentrations equal to and/or less than those dosages approved for human use, PE significantly decreased the signaling activity of the Akt pathway in epithelial cells within 30 min, and induced their atrophy and death within 24 h of exposure. Further, PE is known to penetrate the skin when topically applied, having a dermal resorption rate of about 45% in humans – meaning 45% of PE applied topically travels through the skin into the blood (Eckert et al, 2025).

Summary

The use of gluconolactone and sodium benzoate together as an antimicrobial preservative system for skin care not only provides safe and effective, broad-spectrum effects, the combination also provides substantial skin care benefits, including moisturization, UV protection, and anti-inflammatory effects. Carefully choosing every ingredient we put into our products is one reason why NeoGenesis products are safe and efficacious.

References

Abd El-Mawla AM, Schmidt W, Beerhues L. Cinnamic acid is a precursor of benzoic acids in cell cultures of Hypericum androsaemum L. but not in cell cultures of Centaurium erythraea RAFN. Planta. 2001;212:288–293.

Brahmachari S et al (2007) Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Modifies T Cells at Multiple Steps and Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis1. J Immunol 1 July 2007; 179 (1): 275–283.

Bemani P et al (2020) In Vitro Effects of Sodium Benzoate on the Expression of T Cells-related Cytokines and Transcription Factors in Adjuvant-induced Arthritis Model. Iran J Allergy Asthma Immunol, May2020; 19(Supple.1):43-54.

Eckert E, Jäger T, Leibold E, Bader M, Göen T, Hiller J. Dermal penetration of 2-phenoxyethanol in humans: in vivo metabolism and toxicokinetics. Arch Toxicol. 2025 Mar;99(3):1095-1103.

Jarząbek-Perz S, Dziedzic M, Rotsztejn H, Kołodziejczak A. Evaluation of the effects of 10% and 30% gluconolactone chemical peel on sebum, pH, and TEWL. J Cosmet Dermatol. 2023; 22: 3305-3312.

Li W et al (2025) Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus.Sci. Transl. Med.17,eadp4447(2025).

Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013 Jun;8(3):739-55.

Misel ML, Gish RG, Patton H, Mendler M. Sodium benzoate for treatment of hepatic encephalopathy. Gastroenterol Hepatol (N Y). 2013 Apr;9(4):219-27

Rezaei N, Amirghofran Z, Nikseresht A, Ashjazade N, Zoghi S, Tahvili S, Kamali-Sarvestani E. In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with Multiple Sclerosis. Immunol Invest. 2016 Oct;45(7):679-91.

Wang J, Yang Liu, Wendy R. Kam, Ying Li, David A. Sullivan, Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells, Experimental Eye Research, Volume 196, 2020, 108057,

Why Use Skin-Derived Adipose Mesenchymal Stem Cell Released Molecules in Skincare – A Teleological Explanation

Adipose mesenchymal stem cells (ADSCs) have evolved to arise in the skin during the third trimester of fetal development. These cells arise just before birth so that they can be present following birth to tampen inflammation that may arise in the baby’s new hostile, non-sterile environment where the skin is under constant insult from injuries, toxins, UV, antigens, and pathogens. It’s why ADSCs and the molecules they release are preferred over, 1. bone marrow mesenchymal stem cells and platelets, which serve to induce inflammation and rapid fibrotic scarring, and 2. over umbilical cord mesenchymal stem cells, that have evolved to operate in the sterile conditions of the womb to form the cord, which is unlike skin structure and function, and since it’s a sterile environment, not dampen inflammation which is unneeded and doesn’t happen in the sterile environment where infection can’t happen. The molecules released from ADSCs are the safest and most effective stem cell released molecules to use as skin therapeutics.

Scientist think teleologically often. It’s one of the ways we reason through the discovery and invention of phenomenon. Teleology is relating to or involving the explanation of phenomena in terms of the purpose they serve rather than of the cause by which they arise. In other words, teleology or finality is a branch of causality giving the reason or an explanation for something as a function of its end, its purpose, or its goal, as opposed to as a function of its cause. Why is this thing present, what is it doing?

Adipose mesenchymal stem cells (ADSCs) have evolved to arise in the skin during the third trimester of fetal development and to be present throughout adult life. These cells arise just before birth. So the teleological questions are, why do they arise just before birth, and what are the doing in the adult skin during a person’s lifetime?

Teleologically thinking, the ADSCs are present following birth to tampen inflammation that may arise in the baby’s new hostile, non-sterile environment that presents after birth. The ADSCs arise as tissue specific stem cells in the skin that has developed during the third trimester. The stem cell niche of the skin will help to direct these ADSCs to develop in a manner that is tissue specific and serves to resolve inflammation in that adult skin. This sort of tissue specific development of the ADSCs doesn’t happen in the bone marrow or the umbilical cord, for example. Following birth, the skin is under constant insult from traumatic injuries, toxins, antigens, UV, and pathogens. Those are signals for inflammation. When the skin is compromised by these factors, evolution has given the skin an inflammatory response to fight associated infection. Any of these factors can lead to barrier disruption and an eventual infection, and the inflammatory response is the key to fighting infection. But inflammation is damaging. Not only does infection fight invading pathogens, inflammation also damages our own cells and tissues.

So inflammation has to be tampened, otherwise, if it is prolonged, necroinflammation ensues and our tissues become necrotic or otherwise damaged. Without inflammation being reduced, the damaging inflammatory pathways cause more inflammation and scale-up the damage. And what is present in adult skin to resolve inflammation? It’s the adipose mesenchymal stem cells (ADSCs) and the molecules that they release. In this case, the molecules from ADSCs can help the healing process by a number of mechanisms, including angiogenesis and reducing inflammation. The molecules from ADSCs induce an anti-inflammatory pro-regenerative state in the skin. Diabetic ulcers are example, where the necrotic tissue, such as Necrotizing fasciitis, has to be removed to reduce the inflammation. In these conditions, the ADSCs are no longer present at the site of open wound, and inflammation is hard to control. Addition of ADSC secretome facilitates the healing of the diabetic ulcer through a number of mechanisms, including the reduction of inflammation.

ADSCs are preferred over, 1. bone marrow mesenchymal stem cells and platelets, which serve to induce inflammation and rapid fibrotic scarring, and 2. over umbilical cord or placental mesenchymal stem cells, that have evolved to operate in the sterile conditions of the womb to form the cord, which is unlike skin structure and function, and since it’s a sterile environment, not dampen inflammation.

There’s much hype about cytokines from bone marrow mesenchymal stem cells. I’ve previously blogged about how bad these BMSC molecules are for the skin. Let’s quickly consider inflammation and the stem cells used by AnteAge to make their products: Bone Marrow Mesenchymal Stem Cells (BMSCs), and the molecules they release, prolong and enhance inflammation by increasing survival and function of neutrophils (Castella et al, 2011). Under hypoxic conditions, which induces the activation of TRL4, BMSCs secrete pro-inflammatory factors and decrease the polarization of macrophages from the M1 to M2 phenotype (Faulknor et al, 2017; Waterman et al, 2010). Therefore, BMSCs cultured in normal hypoxic conditions in the laboratory are secreting pro-inflammatory factors and when administered to wounded skin will induce inflammation by recruiting neutrophils and M1 type pro-inflammatory macrophages. When you put AnteAge on your skin, these are the pro-inflammatory molecules damaging your skin.

Safety and efficacy considerations: ADSCs preferred Over BMSCs

I’m asked frequently about the safety of using the molecules from ADSCs, so I’ll address it here. When addressing safety and efficacy concerns of stem cells, we must consider tissue-specific stem cells, first described by Dr. Elly Tanaka, a professor of science at the IMP in Vienna. Choosing the appropriate stem cell type to match the condition to be treated is critical not only to efficacy, but most importantly, safety of the therapeutic. Beyond the genetic and epigenetic factors that influence stem cell phenotype as embryonic stem cells differentiate into somatic stem cells, the immediate niche of the stem cell will have profound influence on the cell’s phenotype. If your wanting to regenerate skin, then use tissue specific stem cells from the skin. ADSCs and their secretome is efficacious and safe. Even ADSCs from cancer patients can been safely used for therapeutic purposes.

We don’t use umbilical cord mesenchymal stem cells (UMSCs) because they are not tissue specific to the skin, and they didn’t evolve to work in adult tissue where inflammation needs to be inhibited. Bone marrow mesenchymal stem cells (BMSCs) do appear in the skin, but only transiently in the skin during open wounds to close the wound quickly (yielding fibrotic scarring). induce inflammation (destructive to tissue), and cause high rates of proliferation (pro-oncogenic). If you think about it, the BMSCs appear transiently during an open wound to fight infection by inducing inflammation, and closing the open wound quickly by hyper-proliferation of cells. BMSCs and their released molecules didn’t evolve to be present in the skin for long periods of time – only transiently. Applying BMSC molecules for an extended time will induce too much inflammation and too much proliferation, leading to long term inflammation, fibrotic scarring, and a pro-oncogenic state.

Beyond their suboptimal efficacy profile, I’ll briefly explain some of the mechanisms underlying our choice of not using BMSCs because of a poor safety profile. The complexity of the bone marrow (BM) niche can lead to many stem cell phenotypes, whether we consider hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BMSCs). Here I will discuss the properties of BMSCs, not HSCs. Because of the complexity, many BMSC phenotypes exist, including disease causing phenotypes that are varied and hard to distinguish – a part of the problem in using BMSC for therapeutic development. This complication, unlike that for ADSCS, includes recirculated cells, particularly recirculated cancer cells. Once a tumor cell disseminates into the BM, the cancer cell often displays phenotypic characteristics of BMSCs rendering cancer cells difficult to distinguish from BMSCs. BM is a site of BMSCs that may differentiate into HSCs [113] and recirculating blood cells that may differentiate into BMSCs [114,115]. BMSCs are also found outside of the niche in peripheral blood [116] and home into sites of injury [117] and cancer tissue where they are educated into becoming a pro-cancerous phenotype [118]. Recirculated melanoma and myelogenous leukemia cells [119] in BM interact with BMSCs to change the phenotype of the BMSC to one that is cancer promoting by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle [120]. Indeed, melanoma tumor cells start to disseminate to BM during the initial steps of tumor development [121]. In breast cancer patients, detection of recirculated cancer cells that disseminated in BM predicts recurrence of the cancer [122]. Cancer cells can fuse with BMSCs and change their phenotype [123], or release exosomes to change the phenotype of BMSCs to cancer promoting [124]. Indeed breast tumor cells fuse spontaneously with bone marrow mesenchymal stem cells [125]. This fusion may facilitate the exchange of cellular material from the cancer cell to the BMSC rendering the fused cell more oncogenic [126]. Further, others have found the same result of this fusion and exchange of cellular material, which has been found to increase metastasis. For example, Feng et al127,found that human hepatocellular carcinoma cells with a low metastatic potential exhibit a significantly increased metastatic potential following fusion with BMSCs in vitro and in xenograft studies. In the end, the BMSCs and their molecules/exosomes, having been conditioned by tumor cells, were found to increase the probability of cancer in human patients [128]. The various phenotypes of BMSCs, including the cancerous phenotypes are difficult to distinguish [36]. In contrast, even ADSCs derived from cancer patients have been found to be safe for therapeutic development [66].

One of many reasons why ADSCs are preferred compared to BMSCs is that ADSCs express a low level of major histocompatibility complex (MHC) class I molecules and do not express MHC class II and costimulatory molecules. Even the exosomes of BMSCs express MHC class II proteins [129]. These problems in BMSCs are amplified when using donor, allogeneic BMSCs that have been replicated many times, essentially aging the cells, during expansion to develop the therapeutic. This is in contradistinction to ADSCs. Critically, when comparing experimental data of BMSCs to ADSCs from the same human donor, “ADSCs have a “younger” phenotype,” according to stem cell scientists [130]. Indeed, Burrow et al found that BMSCs have, among other negative attributes compared to ADSCs, an increased level of senescence compared to matched ADSCs. Senescent cells develop the senescence-associated secretory phenotype (SASP), a pro-inflammatory set of molecules where the local tissue effects of a SASP or specific SASP components have been found to be involved in a wide variety of age-related pathologies in vivo such as hyperplastic diseases, including cancer [131]. Whereas the use of BMSC transplants has a history of medical adverse events, including the induction of cancer in the recipient (Maguire, 2019), fat grafting, along with its constituent ADSCs, have a long history of safety in medical procedures dating back to 1893 when the German surgeon Gustav Neuber transplanted adipose tissue from the arm to the orbit of the eye in an autologous procedure to fill the depressed space resulting from a postinfectious scar [132]. Fat grafting’s long history of being safe, regardless of the harvesting techniques used in patients [120,133], has been recently reviewed by physician-scientists at Baylor College of Medicine [134]. Furthermore, physician-scientists at Stanford University School of Medicine have recently reviewed the safety and efficacy of using ADSCs to augment the outcomes of autologous fat transfers [135]. 136,have found that ADSCs and fat grafting for treating breast cancer-related lymphedema is safe and efficacious during a one year follow-on, where patient-reported outcomes improved significantly with time. In a randomized, comparator-controlled, single-blind, parallel-group, multicenter study in which patients with diabetic foot ulcers were recruited consecutively from four centers, ADSCs in a hydrogel was compared to hydrogel control. Complete wound closure was achieved for 73% in the treatment group and 47% in the control group at week 8. Complete wound closure was achieved for 82% in the treatment group and 53% in the control group at week 12. The Kaplan–Meier (a non-parametric statistic used for small samples or for data without a normal distribution) median times to complete closure were 28.5 and 63.0 days for the treatment group and the control group, respectively [137]. Treatment of patients undergoing radiotherapy with adult ADSCs from lipoaspirate were followed for 31 months and patients with “otherwise untreatable patients exhibiting initial irreversible functional damage” were found to have systematic improvement or remission of symptoms in all of those evaluated [138]. In animal models with a full thickness skin wound, administration of ADSCs, either intravenously, intramuscularly, or topically, accelerates wound healing, with more rapid reepithelialization and increased granulation tissue formation [139], and topically applied the ADSCs improved skin wound healing by reducing inflammation through the induction of macrophage polarization from a pro-inflammatory (M1) to a pro-repair (M2) phenotype [140]. I’ve discussed some of the other mechanism by which ADSCs reduce inflammation in the skin in a recent blog.

Summary

Adipose mesenchymal stem cells (ADSCs), unlike stem cells from tissues other than the skin (BMSCs and UMSCs) and stem cells from non-adult sources in the womb (UMSCs), evolved to work in the skin of adults to inhibit inflammation and to reset the innate and adaptive immune systems of the skin to a anti-inflammatory, pro-regenerative healing state to maintain and regenerate normal, non-fibrotic skin structure and function.

Skin Care Misinformation and Hype – Penn Smith Misinforms About Exosomes in ReVive

I was made aware of a YouTube video that compared a product I developed at NeoGenesis to a product manufactured for ReVive. Always looking forward to learning new things, I had a look at the video. Penn Smith is not a name I recognized, so I looked her up.

The first thing I learned is that she works for Jeff Bezos at Amazon, selling products for the skin.

Notice I didn’t say “skincare products.” I said products for the skin. Why? Look at the first product I saw her selling:

She’s selling a product with Diazolidinyl urea, which is an antimicrobial preservative that works by forming formaldehyde in cosmetic products. People exposed to such formaldehyde-releasing ingredients may develop a number of problems, including contact dermatitis, allergy and cancer. PEG is a poor choice too – causing contact dermatitis. Daily cleansing with such a product is really a very poor choice.

And here is Penn smith selling a product for Amazon that she says “I haven’t tried it.”

Salespeople who are informed and educate us, and make thoughtful recommendations are very important. That’s not what she’s doing – first she’s selling something detrimental to our health, and in the second instance she’s selling something of which she knows nothing. I could go on, but let’s look now at the product she is comparing to Recovery by NeoGenesis, the technology (S2RM) and product that I developed. BTW, I’m a scientist and have many peer reviewed, PubMed listed science articles supporting what I’m saying (some of my articles are here, and my scientifically reviewed book is here).

Here’s the Recovery product that I developed with the S2RM technology that I started developing while a professor at the University of California, San Diego. It has been a long journey coming to the point where I could develop this technology, and many people along my journey have taught me so much – I pay tribute to all those who helped me, including our team at NeoGenesis.

Let’s now look at the product Penn Smith is selling – ReVive Ultimate Serum.

I looked at the ingredients of this product and was taken aback by how poor, whomever formulated it, the formulator performed. Why would a company cheapen its products. So I had a look at the company. ReVive Skincare is owned by a private equity group called Tengram Capital Partners, a PE firm led by Willam Sweedler, a group with financial troubles. They have a huge amount of debt and are therefore selling-off portfolio companies and cutting costs at the companies they still own. The ReVive Ultimate Serum formulation is one means by which they are cutting cost. If you’d like to learn how private equity is stripping the quality of companies and their products, two good books provide some of the details, including one by Gretchen Morgenson.

Now to the product. Penn Smith calls Ultimate Serum, “A dupe for TNS.” Yes, she calls it a “dupe.” Of course the definition of “dupe” is to trick or deceive. So apparently Penn Smith has been hired by a private equity group to sell a “dupe.”

Looking at the ingredients in ReVive Ultimate Serum, I can tell you why this product is not as good as SkinMedica TNS or NeoGenesis Recovery.

Poor choice of ingredients in this product include:

1.Tetradecyl Aminobutyroylvalylaminobutyric Urea Trifluoroacetate – EWG = 10 (https://www.ewg.org/skindeep/ingredients/862173-TETRADECYL_AMINOBUTYROYLVALYLAMINOBUTYRIC_UREA_TRIFLUOROACETATE/)

Common concerns (from EWG)

See how this product scores for common concerns.

  • MODERATE – Cancer
  • HIGH – Allergies & Immunotoxicity
  • HIGH – Developmental and Reproductive Toxicity
  • HIGH – Use Restrictions

2. Bone Marrow Mesenchymal Stem Cell exosomes (BMSCe) are a poor choice, including because of oncogenic potential of their exosomes – see the following paper, section “Safety and efficacy considerations: ADSCs preferred Over BMSCs” – (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437473/),

3. Isolated exosomes have been lyophilized (freeze drying procedure) that renders suboptimal exosomes with damaged proteins in the core, and denuded (stripped away) proteins and polysaccharides on its surface (https://drgregmaguireskincare.blog/2023/06/18/why-neogenesis-doesnt-lyophyilize-freeze-dry-our-secretome-exosome-s2rm-fresh-is-better/). It’s a cheap way to have exosomes in your product, and private equity likes cheap. They don’t work well though.

4. Many of the active molecules in conditioned media from stem cells are in the soluble fraction, not in the exosomes. Using the soluble fraction in combination with exosomes is optimal – it’s more expensive to do it this way, but much more efficacious (see, for example, https://www.sciencedirect.com/science/article/pii/S1529943022000353#bib0035). The soluble fraction contains many molecule types, including small heat shock proteins (sHSP) that repair other proteins and fatty acids that inhibit COX-2, reducing pain and inflammation.

5. Polysorbate 20 – skin irritant, there are better choices for emulsification

6. Butylene glycol – again, a skin irritant, better choice are available

7. Pentylene glycol– another irritant

If you add a number of skin irritants to the formula, and have people use it daily, it’s obviously a sub-optimal product. And comparing cheap freeze dried exosomes from bone marrow stem cells to the molecules used in SkinMedica TNS (from fibroblasts) and NeoGenesis (from fibroblasts and skin derived mesenchymal stem cells) that haven’t been damaged and aren’t derived from dangerous bone marrow cells shows her ignorance and/or duplicity.

It cost more to use fresh exosomes that haven’t been damaged by freeze drying, something private equity doesn’t like to pay for, but companies using this technology have much better technology and more effective products.

Suboptimal Exosome Product Brought to Market By Failed Company – Benev, and Another Local Company – Invitrx

Failed company brings suboptimal skincare product to market by a manufacturer in Korea, known for fraudulent and corrupt stem cell science, even at it’s premier university, Seoul National University.

Benev is a company that couldn’t survive in the market, and had numerous problems as exemplified by this FDA review where they found poor quality control and the use of expired materials being used in production:

http://fda-warning-letters.blogspot.com/2010/06/benev-company-inc.html

For example, Benev was using expired ingredients to manufacture drugs that went to market, and falsified documents to hide their egregious behavior (below is from a FDA Warning Letter to Benev):

“QCD” refers to Benev’s quality control department.

As a consequence of this violation, and may other violations, FDA concluded that Benev’s drug products were adulterated:

Resulting from continued poor performance, Benev sold themselves to a Korean company, ExoCoBio, that uses Benev to sell exosomes in the USA. A culture of corruption and fraud was highlighted by the veterinarian, Hwang Woo-suk, and his many conspirators who faked a landmark stem cell publication. That culture was exported to the USA by Benev. Previously, Benev worked with another local company called Invitrx, a company with a rich history of FDA violations, a long history, and led by a man, Habib Torfi, known for delivering stem cells to patients in a grocery bag.

There are numerous problems with what Benev (ExoCoBio) is doing to exosomes.

First, exosomes are only a fraction of what stem cells release, and without the non-exosomal fraction being combined with the exosomes, suboptimal results are achieved. In other words, when the exosomes aren’t isolated but are combined with the soluble fraction as is natural when the stem cells release their molecules, the results are superior to using only the isolated exosomes.

Second, they lyophilize their exosomes – this is a freeze-drying process that damages the molecules inside the exosome, and molecules attached to the outside of the exosome. Basically this harsh process removes all the water from the product, leaving a small amount of dry powder. The powder is full of damaged proteins and other molecules. Lyophilization leads to aggregation of proteins and their denaturization. “Unfortunately, the lyophilization process generates both freezing and drying stresses, which can denature proteins to various degrees” (Wang, 2000). Protein denaturation refers to the loss of biological activity through changes of the specific spatial conformation of protein in certain physical or chemical factors, resulting in the change of physical and chemical properties.

Lyophilization is used for the convenience of the company – it’s easier to store and ship a small pellet of lyophilized powder than it is to store and ship fresh, undamaged exosomes contained in their original solution.

From the Benev website we see they’re using lyophilized exosomes, and only the exosomes without the benefit of the soluble fraction (the overlapping text on their website is another example of the lack of attention to detail in this failed company):

To compare, NeoGenesis uses fresh (not damaged from freeze-drying) S2RM that contains both the 1. exosomal fraction, and 2. soluble fraction. Also, NeoGenesis uses both fractions from 3 cell types derived from the skin (mesenchymal stem cells and two types of fibroblasts). In contrast, Benev uses only a portion of the molecules released from one cell type, yielding a much depleted set of molecule types compared to NeoGenesis, many of which are damaged by Benev using  lyophilization. 

Another nearby company, Invitrx, in Lake Forest, is selling non-sterile exosomes for injection – allogenic injection. Talk about dangerous. Invitrx has a long history of unsafe practices. For example, illegally selling stem cells for injection, delivered in a paper grocery bag and selling non-sterile exosomes to physicians as exemplified in this FDA 486 Warning Letter, in which the agency details numerous non-sterile practices used to produce their exosomes.

You can read about the problems with lyophilization with many references to the published literature in my blog:

Why NeoGenesis Doesn’t Lyophyilize (Freeze Dry) Our Secretome/Exosome S2RM – Fresh is Better

Safety and Efficacy Considerations of Stem Cell Technologies for Skin Care: : ADSCs preferred Over BMSCs

Mesenchymal Stem Cells and their Progenitor Cells (Fibroblasts) Derived from Skin are Superior to Bone Marrow Derived Mesenchymal Stem Cells

When addressing safety and efficacy concerns of stem cells, we must consider tissue-specific stem cells. Choosing the appropriate stem cell type to match the condition to be treated is critical not only to efficacy, but most importantly, safety of the therapeutic. Beyond the genetic and epigenetic factors that influence stem cell phenotype as embryonic stem cells differentiate into somatic stem cells, the immediate niche of the stem cell will have profound influence on the cell’s phenotype. Therefore, the appropriate use of adipose derived mesenchymal stem cells (ADSCs), and their related progenitor cells from the skin, fibroblasts, is optimal for skin care compared to bone marrow mesenchymal stem cells (BMSCs)

Let’s consider some of the problems BMSCs pose for developing skin care products. The complexity of the bone marrow (BM) niche can lead to many stem cell phenotypes, whether we consider hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BMSCs). Here I will discuss the properties of BMSCs, not HSCs. Because of the complexity, many BMSC phenotypes exist, including disease causing phenotypes that are varied and hard to distinguish – a part of the problem in using BMSC for therapeutic development. This complication, unlike that for ADSCS, includes recirculated cells, particularly recirculated cancer cells. Once a tumor cell disseminates into the BM, the cancer cell often displays phenotypic characteristics of BMSCs rendering cancer cells difficult to distinguish from BMSCs. BM is a site of BMSCs that may differentiate into HSCs and recirculating blood cells that may differentiate into BMSCs [see Cardenas et al; Tondreau et al]. BMSCs are also found outside of the niche in peripheral blood and home into sites of injury and cancer tissue where they are educated into becoming a pro-cancerous phenotype. Recirculated melanoma and myelogenous leukemia cells in BM interact with BMSCs to change the phenotype of the BMSC to one that is cancer promoting by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle. Indeed, melanoma tumor cells start to disseminate to BM during the initial steps of tumor development. In breast cancer patients, detection of recirculated cancer cells that disseminated in BM predicts recurrence of the cancer. Cancer cells can fuse with BMSCs and change their phenotype, or release exosomes to change the phenotype of BMSCs to cancer promoting. Indeed breast tumor cells fuse spontaneously with bone marrow mesenchymal stem cells. This fusion may facilitate the exchange of cellular material from the cancer cell to the BMSC rendering the fused cell more oncogenic. Further, others have found the same result of this fusion and exchange of cellular material, which has been found to increase metastasis. For example, Li et al found that human hepatocellular carcinoma cells with a low metastatic potential exhibit a significantly increased metastatic potential following fusion with BMSCs in vitro and in xenograft studies. This means that the BMSCs and their molecules/exosomes, having been conditioned by tumor cells, were found to increase the probability of cancer in human patients. The various phenotypes of BMSCs, including the cancerous phenotypes are difficult to distinguish. In contrast, even ADSCs derived from cancer patients have been found to be safe for therapeutic development.

One of many reasons why ADSCs are preferred compared to BMSCs is that ADSCs express a low level of major histocompatibility complex (MHC) class I molecules and do not express MHC class II and costimulatory molecules. Even the exosomes of BMSCs express MHC class II proteins. These problems in BMSCs are amplified when using donor, allogeneic BMSCs that have been replicated many times, essentially aging the cells, during expansion to develop the therapeutic. This is in contradistinction to ADSCs. Critically, when comparing experimental data of BMSCs to ADSCs from the same human donor, “ADSCs have a “younger” phenotype,” according to stem cell scientists. Indeed, Burrow et al found that BMSCs have, among other negative attributes compared to ADSCs, an increased level of senescence compared to matched ADSCs. Senescent cells develop the senescence-associated secretory phenotype (SASP), a pro-inflammatory set of molecules where the local tissue effects of a SASP or specific SASP components have been found to be involved in a wide variety of age-related pathologies in vivo such as hyperplastic diseases, including cancer. Whereas the use of BMSC transplants has a history of medical adverse events, including the induction of cancer in the recipient (Maguire, 2019), fat grafting, along with its constituent ADSCs, have a long history of safety in medical procedures dating back to 1893 when the German surgeon Gustav Neuber transplanted adipose tissue from the arm to the orbit of the eye in an autologous procedure to fill the depressed space resulting from a postinfectious scar. Fat grafting’s long history of being safe, regardless of the harvesting techniques used in patients, has been recently reviewed by physician-scientists at Baylor College of Medicine. Furthermore, physician-scientists at Stanford University School of Medicine have recently reviewed the safety and efficacy of using ADSCs to augment the outcomes of autologous fat transfers. Scientists have found that ADSCs and fat grafting for treating breast cancer-related lymphedema is safe and efficacious during a one year follow-on, where patient-reported outcomes improved significantly with time. In a randomized, comparator-controlled, single-blind, parallel-group, multicenter study in which patients with diabetic foot ulcers were recruited consecutively from four centers, ADSCs in a hydrogel was compared to hydrogel control. Complete wound closure was achieved for 73% in the treatment group and 47% in the control group at week 8. Complete wound closure was achieved for 82% in the treatment group and 53% in the control group at week 12. The Kaplan–Meier (a non-parametric statistic used for small samples or for data without a normal distribution) median times to complete closure were 28.5 and 63.0 days for the treatment group and the control group, respectively. Treatment of patients undergoing radiotherapy with adult ADSCs from lipoaspirate were followed for 31 months and patients with “otherwise untreatable patients exhibiting initial irreversible functional damage” were found to have systematic improvement or remission of symptoms in all of those evaluated. In animal models with a full thickness skin wound, administration of ADSCs, either intravenously, intramuscularly, or topically, accelerates wound healing, with more rapid reepithelialization and increased granulation tissue formation, and topically applied the ADSCs improved skin wound healing by reducing inflammation through the induction of macrophage polarization from a pro-inflammatory (M1) to a pro-repair (M2) phenotype.

All in all, companies using BMSCs to develop their skin care products demonstrates a profound ignorance of the related science. Incompetence, and a greedy, lazy approach to serving the skin care market is demonstrated by those using bone marrow stem cells to develop skin care products that potentially damage their clients.

NeoGenesis S2RM Technology

Stem cells in the skin are cells that self-renew themselves, so that they are always present in the skin. While stem cells in the skin can generate other cell types, their most important function is to continuously release molecules into the skin. Many types of molecules are released into the skin by the stem cells, the function of which is to maintain and heal the skin throughout our lives.

NeoGenesis’ S2RM technology uses all the different molecules from stem cells derived from the skin, instead of just one or a couple of molecules. S2RM technology therefore targets multiple pathways underlying a disease or condition, not just one or a few pathways as used in previous therapeutic designs. The condition, for example, can be aging, where the pathways in the skin are not working as well as they once did when the skin was young. The multiple molecules renormalize the multiple pathways and thus renormalize the physiology of the skin. For aging skin, this means the pathways are now working more like they did when we were younger. Simply put, diseases and conditions of the skin have many unique abnormal pathways that underlie the condition, and each unique pathway must be renormalized using many molecule types, each of which acts at one of the many abnormal pathways underlying the disease or condition.

Specifically, NeoGenesis uses proprietary and patented adult stem cell released molecules in its safe and effective core technology. The molecules are released, not extracted, from 3 or more types of adult stem cells derived from the skin to make our products. Using released, not extracted, molecules assures that the molecules are fully formed in their natural state and therefore effective, and naturally packaged into a protection and penetration liposome-like structure called the exosome. The exosome is like a tiny capsule, such as that used to encapsulate drugs. However, unlike the capsule, mother nature has designed the exosome to be smart. It has special structures that allow it to easily penetrate the skin and deliver the molecules where they are needed. Further, we don’t use immortalized cells that may secrete pro-oncogenic signals in their exosomes, and may also produce exosomes with an altered content, rendering them less efficacious.

Adult stem cells are partially differentiated stem cells, not embryonic stem cells. This means that the adult stem cells used by NG are more mature than embryonic stem cells, which are cells that can make any cell in the body. The adult stem cells are lineage restricted, meaning that the stem cells we use that are derived from the skin only make skin cells. Skin specific adult stem cells developed in the skin to specifically and effectively maintain and heal the skin. Because adult stem cells are tissue specific, stem cells derived from the skin work better than other types of stem cells from other parts of the body in their effectiveness to maintain and heal the skin. For example, adult stem cells derived from bone marrow don’t work well in the skin.

Key to how adult stem cells work before they differentiate into mature skin cell types is that the adult stem cells reside in the skin to maintain and heal the skin, doing so by releasing building block molecules such as collagen and laminin, and instruction set molecules, such as HAPLN-1, that signal the building block molecules how to organize. Molecules, such as HAPLN-1, decrease in concentration as we age, and as a result diseases, such as melanoma, will occur with a greater probability. From the work of Dr. Ashani T. Weeraratna, Ph.D. at Johns Hopkins, we know that supplying HAPLN-1 to aged skin can reverse this effect, and renormalize the matrix and lymphatic system in the aged skin. As she has pointed out, normal matrix in the skin is vital to good health and keeping skin cancer at bay. This follows the pioneering work by Dr. Mina Bissell, Ph.D. at Berkeley, who taught us all how critical the matrix is to cancer formation, and as I have pointed out, to many other diseases.

The NeoGenesis S2RM technology is a combination of adult stem cells of different ages where younger adult stem cells are used to make the building block molecules for scar-free healing, and slightly older stem cells make the instruction set molecules so that normal, adult skin architecture is maintained or reformed after injury. The molecules in S2RM also include those that calm inflammation and help to reset our skin’s immune system to help repair the skin. Other molecule types are present that repair damaged proteins in the skin, while other molecules prevent and repair damage to protein, lipids, and DNA.

Because we use multiple skin stem cell types, from which we collect all the molecules released, NeoGenesis’ S2RM is the most advanced skin technology available in today’s skin care market.

S2RM Contains Protein, Lipids, Micro-RNA, and No DNA.

The stem cell released molecules that NeoGenesis uses in our S2RM technology is a mixture of proteins, micro-RNA and lipids that is from skin derived mesenchymal stem and progenitor cells. This technology is a new means for therapeutic development. The molecules that are released from the different stem cell types are largely packaged into exosomes. Exosomes under 150 nm in diameter do not contain DNA, whereas larger extracellular vesicles (EVs) can contain small amounts of DNA. Exosomes are made by cells in different process than the way EVs are made. As with other studies characterizing vesicles secreted from mesenchymal stem cells, we have found the size of the exosomes (small extracellular vesicles) to about 50-80nm in diameter. Again, these exosomes have not been found to contain DNA. At NeoGenesis, we also use filtration methods in the production of the S2RM that would prevent large EVs from entering our S2RM. As stated by Rani et al (2015), “the fundamental basis for MSC-EV therapeutic effects lies in their ability to transmit biological information—in the form of proteins, glycoproteins, lipids, and ribonucleic acids—from stem cells to injured cells.” This is an important part of the exosomal S2RM technology, but there is more. The S2RM is also, 1. immune modulating to bias towards tissue repair and away from inflammation, 2. supplies important building blocks for tissue repair, such as collagen, 3. many types of antioxidants to help repair and protect proteins, DNA, and lipids, and 4. supplies proteosomes to carry away damaged cells for recycling. Attributes one through four are in addition to the repair properties of the S2RM that include growth factors, and heat shock proteins to repair proteins and DNA. Important to note is that the exosomes work in concert with soluble proteins to repair tissue – it’s not just the exosomes. This is why NeoGenesis uses the exosomes and the soluble proteins (the fraction of proteins not contained in the exosomes) in our S2RM technology. – we don’t through away the good and synergistic part of what stem cells release, a fraction of the S2RM that contains many proteins, including heat shock proteins. The fraction not contained in exosomes also contains many important signaling lipids that reduce inflammation, such as PEA, and that build the extracellular matrix. And it’s also important to note the cells we use from the skin are superior in this regard, and may others ways too, than the mesenchymal stem cells from bone marrow.

Why NeoGenesis Formulates and Manufactures its Own Products and Dosen’t Use Contract Manufacturers

Quality control, efficacy, safety, and the production of novel products is key to doing it ourselves

NeoGenesis is a vertically integrated company that formulates, manufactures, and sells skin care products, including those classified as drugs and cosmetics. We even make our own stem cell released molecules in a high level biotech facility on site. Many reasons lead NeoGenesis to formulate and manufacture our products within our own facilities. For example, when I created the S2RM technology, no one else on the planet was making such an ingredient, let alone even knew what it was. This is a new type of active ingredient that had to be developed and then scaled for commercial production. We had to do it ourselves at NeoGenesis because no one else knew how to do it. This is still the case.

Here’s another reason we don’t use contract manufacturers that’s often not considered. Having our own manufacturing facility means that our products are not cross-contaminated with chemicals that we don’t want in our products for safety and efficacy reasons. This’s what often happens when small companies employ a contract manufacturer. One company will be producing a product with, for example, parabens, which are endocrine disruptors, and those parabens will be included in a company’s products who doesn’t want them because of cross contamination. At NeoGenesis, we don’t use parabens and so there is no chance of cross contamination

Little things are important when formulating. For example, we don’t use coconut oil in our products because it’s comedogenic -it clogs pores. I’ve recently formulated a mineral sunscreen that doesn’t use coconut oil or the ingredient BOS (Butyloctyl salicylate) as do many other companies. Why? Because BOS is a salicylate. And salicylates convert back to salicylic acid when they’re metabolized in the skin and other parts of the body, making them potentially toxic, especially for pregnant women. And children shouldn’t be exposed to salicylates at any concentration. Remember, children are undergoing rapid development, and toxins can negatively perturb developmental pathways potentially leading to life-long disease. Salicylic acid is a drug regulated by the FDA. For good reason, because it is easily systemically absorbed by the body and can be toxic. Children under 2 yrs should not use it. Unfortunately common in the chemical industry is that some companies will slightly modify a compound’s structure such that the altered substance stealthily flies under the radar of overwhelmed regulators, such as the FDA. BOS is one of those ingredients.

When Neogenesis formulates and manufactures our products, we know what’s in our product. Many contract manufacturers will source the lowest cost ingredients possible, and the formulations will also be made with the profit in mind first, over quality. Some will leave out an expensive ingredient to cut their cost of manufacturing and increase their profit. Some companies have been caught adding drugs, such as steroids, to their cosmetic products without disclosing these possibly dangerous chemicals to their customers.

Another aspect of being a vertically integrated company is that we control our sales and marketing. The narrative we tell is our own, and won’t be some made-up fictious story making wild claims that aren’t true. When we sell a product to someone it is meant to be beneficial to them, and not simply to take their money. As my father always taught me, if you take someone’s money, you need to give them something of value in return. Not every product that we make and sell will be right for a particular person – at NeoGenesis we let you know what is best for your skin and what may not be useful for you.

There are a number of ethical companies in the skin care industry – chose carefully, because some, such as Cosmetic Innovations in Texas, are not.