While matrikines from damaged tissue increase inflammation, matrikines from adipose mesenchymal stem cells (ADSCs) and fibroblasts (FBs) reduce inflammation and rebuild the matrix without fibrosis.
The global aging of populations has driven a steady rise in skin pathologies — including skin cancer, inflammatory dermatoses, photoaging, and chronic wounds — imposing a growing burden on healthcare systems and quality of life (Flohr & Hay, 2021). Addressing these conditions requires not only early detection, effective therapeutic strategies tailored to the aging skin environment, but most importantly, improved prevention strategies.
Central to the pathology of most skin conditions, indeed, most tissues (Maguire, 2018), is the extracellular matrix (ECM) — a dynamic network of proteins, proteoglycans, and associated molecules that provides structural support, maintains tissue integrity, and governs cell migration, proliferation, differentiation, and survival (Bhat and Bissell, 2014; Kular et al., 2014). The ECM is maintained through continuous, protein- and tissue-specific cycles of synthesis and degradation; disruption of this homeostasis underlies both pathological conditions and the aging process itself (Iozzo & Gubbiotti, 2018; Statzer et al., 2023).
Enzymatic degradation of ECM macromolecules liberates small bioactive peptides known as matrikines, which exert broad (patho)physiological effects on cell signaling, behavior, and tissue homeostasis. The term was introduced by Maquart et al. to describe peptides released by partial proteolysis of ECM components that retain the capacity to regulate cellular activity (Maquart et al., 2004). I’ve adopted the expanded definition of Gaggar and Weathington, which requires matrikines to satisfy three criteria: (1) they are derived from larger ECM macromolecules; (2) they are generated by enzymatic, chemical, or other cleavage — and can therefore be produced ex vivo and introduced therapeutically; and (3) they display intrinsic bioactivity on cells or cellular receptors, independent of the properties of their parent molecule (Gaggar & Weathington, 2016).
In skin, matrikines have been identified across a range of pathological contexts, including melanoma, wound healing, inflammatory disease, and aging (Jariwala et al., 2022; Sivaraman & Shanthi, 2018). Their therapeutic potential is substantial: matrikines have been shown to accelerate wound closure by promoting cell migration and ECM deposition, attenuate inflammation through modulation of cytokine production, and counter skin aging by stimulating collagen synthesis. However, during chronic injury, uncontrolled release of matrikines can drive fibrotic cascades by activating fibroblasts and triggering the abnormal deposition of collagen, worsening tissue scarring. Cutaneous matrikines as produced in damaged skin is a complex process, encompassing their ECM precursors, pharmacological activities, roles in skin pathology, and prospects for therapeutic application. But overall, these matrokines produced in damage skin are, of course, damage signals. As such, they differ from the marix building molecules, including matrikines, released from stem cells resident in the skin. For example, the tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant; meaning it is an inflammatory matrikine. Conversley, the molecules released from skin derived stem cells contained in NeoGnesis S2RM, are anti-inflammatory (Maguire et al, 2026).
Matrikines produced from the proteins released from stem cells is a developmental process, not a damage signaling process. These molecules, including matrikines or their precursors (such as procollagen), released from skin stem cells are anti-inflammatory, which is unlike the matrikines produced in damaged skin.
A buzz has been created for matrikines in skincare, but remember, matrikines produced by damaged matrix in the skin are on the whole pro-inflammatory. However, the secretome from ADSCs and FBs, as used in NeoGenesis’ S2RM technology, has been found to be anti-inflammatory and does so by containing a plethora of proteins and microproteins, all of which contain mutliple peptide sequences, including matrikines. Rebuilding the skin’s matrix is critical to skin health, and the best products on the market to help rebuild the matrix and reduce fibrosis are those that contain the S2RM – Recovery, Skin Serum, and Booster from NeoGenesis. Using NeoGenesis’ S2RM-based products can prevent inflammation and scarring that occurs as the skin ages and is bombarded by inflammatory damage-associated matrikines, promoting skin longevity.
Adding life to years is a paradigm shift that has given rise to a new concept: healthspan — Increasing the length of time a person can live in good health, with physical, cognitive, emotional resilience, and a feeling of well being.As the largest organ in the body, and in bidirectional communication with the whole body, skin health not only reflects systemic healthspan, but is partially causative in systemic healthspan.
Research into exceptional longevity has revealed a critical insight: Healthy aging is not defined by preserving a “young” phenotype, but by sustaining stable, resilient, and well‑adapted cells and tissues over time.Recent data and new conceptualizations have fundamentally reframed how we think about both aging and intervention. In this paradigm shift, healthspan is not simply about preserving youth, rather it is about supporting healthy biological adaptation over time. Therefore, instead of “anti-aging,” the new rubric is “longevity.” For decades, the concept of longevity was commonly framed narrowly, as “how long can we live?” Now, that question feels incomplete and not aligned with how people experience aging. Healthy aging is no longer about reacting to decline, rather sustaining healthspan during an increased lifespan is what we now consider.
Considering the skin, this means using products with efficacy, not just coverups and quick fixes. Many products will use ingredients that fill lines and wrinkles and use minerals to even the skin tone, neither of which impart health to the skin – they’re just coverups. Other products reduce lines and wrinkles for a few hours by stretching the skin and, again, impart nothing healthy to the skin. Instead, look for products that are backed by science and use proper laboratory engineering technolgies that bring health to the skin. Healthy skin is beautiful skin. Is every ingredient in the product chosen carefully? Some products will include efficacious ingredients, but then chose other ingredients that negate the efficacy of that carefully chosen ingredient. Case in point – how many times have I seen what could have been a good product given efficacious ingredients, but they negate the positive by using ingredients like phenoxyethanol.
Preventing and attenuating cellular senescence (senomorphics) is now a key consideration in scientific study, and indeed, in skin care. But science takes a back seat on the internet. Instead of science, the “clipping economy” has become the backbone of the entire internet. Cheaper than traditional advertising, and often spewing fake science, people and companies employ bots and paid users to generate fake hype for everything from government to supplements to skin care. The internet has become so saturated with this fakery that now almost everyone has to do it to compete. But I don’t. My blog is not glossy and full of fakery, rather it’s didactic. That’s why professionals in the skin care industry reach out to me for my expertise.While not using clickbait and hype means my viewership is low, but what I deliver to the reader is high quality and based on evidence and rational thought. Whether it’s using my patented S2RM technology for skincare or nervous system repair, our technology at NeoGenesis is a paradigm shift in healthspan technologies.
Some of the mechanisms by which NeoGenesis Recovery helps to optimize skin longevity (Picture by Kevin Wiener of NeoGenesis).
Whether it’s the dermis and its rich extracellular matrix, barrier function, or the skin’s microbiome, all must be optimized for healthspan and lifespan. NeoGenesis features technologies that I developed in our laboratories; technologies that improve the structure and function of the dermis and its rich extracellular matrix, barrier function, and the skin’s microbiome.
As a professor of neuroscience, I give an example of bidirectional communication between skin and brain. Within the skin–brain connection, psychological stress triggers neuropeptide release from the brain that exacerbates inflammatory skin conditions such as psoriasis. Conversely, chronic skin inflammation signals back to the brain these inflammatory messages, influencing neural development and behavior.
As a consumer, if you are overwhelmed by the constant churn of product launches, look no further than the S2RM technology. I launched the technology in 2010 with BioRegenerative Sciences, and that morphed into a consumer-friendly technology at NeoGenesis in 2014. S2RM is a natural, exosome and secretome-based multifunctional product using the molecules secreted from skin stem cells. While so-called discovery of new ingredients, often only the discovery of a new way to offer marketing hype, once drove excitement in the market, now it’s creating consumer fatigue. People are choosing fewer products, products that work, gravitating toward products with clear purpose, multifunctionality and proven results. Skin minimalism is no longer a trend, it’s becoming a mindset. NeoGenesis Recovery is the ultimate in skin minimalism by using one product that contains hundreds of natural stem cell derived proteins that target hundreds of pathways simulataneously to yield long term efficacy and optimizing skin longevity.
Stay with me in my blog, I’ll have more to say about how NeoGenesis Recovery reduces skin inflammation leading to improved longevity, how Barrier Renewal Cream rebuilds barrier function to reduce inflammation and improve longevity, and MB-2 and MB-1 to restore the microbiome – a very important part of skin longevity.
Harnessing and mimicking the skin’s innate, adaptive ability to detect, process, and respond to environmental stimuli and internal signals to maintain its optimal condition.
Science-backed efficacy and safety, sensorial experiences, and natural, skin-identical ingredients are core to NeoGenesis’ technology. Ours is a holistic approach, a systems-therapeutic (Maguire, 2014) approach to skin care, using multifunctional ingredients and products that address both physical appearance and underlying health. Healthy skin is beautiful skin. Dr. Maguire’s revolutionary approach at NeoGenesis is explained in his academic book, “Adult Stem Cell Released Molecules: A Paradigm Shift to Systems Therapeutics” (Nova Science Publishers, 2018); his popular book, Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts (Amazon, 2020), and has garnered interest for years by those in the skin care industry.
Aesthetic treatments have become increasingly destigmatized, as skin experts and influencers sharing these interventions online becomes the norm. These treatments once exclusive to the clinic are now reshaping expectations at home, as demand grows for powerful at-home alternatives delivering visible results – winning on time, budget, ease of use, and of course results. But this shift isn’t just about DIY. It’s about medical-like performance without the costs and negative side-effects. Ingredients mimicking the mechanisms and outcomes of aesthetic procedures are gaining traction — offering smoother, firmer, more volumized skin without a needle in sight. And with nutrition, including caloric restriction, being top of mind, consumers increasingly seek safer, accessible alternatives to GLP-1 medications that mirror or improve their benefits. The result? Skin care that goes beyond hydration, cover-up, or smoothing. NeoGenesis performs like a procedure – delivering clinic-coded results, at home. Those using GLP-1 agonists, for example, will benefit from using NeoGenesis Recovery to remediate the negative consequences of the GLP-1 agonists on the fibroblast and ADSCs in the skin.
Longevity
Longevity has emerged as a central focus in health and beauty, as consumers increasingly seek ways to biohack their bodies for long-term results. This shift from traditional anti-ageing toward a lifespan- and healthspan-driven approach focuses on biological age and prolonging skin life at the cellular and tissue levels, for example, fibroblasts and the extracellular matrix —addressing the root causes of aging. At the same time, the longevity culture strives in lifestyle changes to achieve a healthy mindset and appearance. In line with this trend, the biohacking industry is gaining momentum and can become more accessible due to the “information age.” NeoGenesis is an important part of skin “biohacking,” in the best sense of the word by bridging science, technology, and self-optimization.
Biohacking can include stem cell released molecules (S2RM or S3RM) applied to the skin yielding renewed and optimized mitochondrial function (picture from Kevin Wiener).
Dr. Greg Maguire, Ph.D. – NeoGenesis Cofounder – Top 2% of Scientists
Dr. Greg Maguire of NeoGenesis has a long history in physiology and functional medicine (Maguire, 2013), and his methods for biohacking (Maguire, 2020) are helping to shape a new, performance-driven vision of long-term skin and body care. Whether it’s secretome and exosome technology, naturally sourced skin-identical nutrients as ingredients, or microbiome renormalization using prebiotics, probiotics, and postbiotics (Maguire and Maguire, 2017; 2019), Maguire has introduced these concepts and technologies to skin care.
Dr. Greg Maguire is one of the world’s leading scientists, having an H-index of 41. An H-index of 41 places a researcher in the top 2% of most-cited scientists globally. While precise percentiles fluctuate by field and database, this score is consistently categorized as “outstanding” and is indicative of a scholar at the highest levels of academia.
Web of Science for Dr. Greg Maguire, H-index = 41, placing Dr. Maguire in the top 2% of scientists world-wide.
NeoGenesis is pioneer in science-based dermohacking and continues to harness this disruptive vision by bridging longevity science, nature, and premium skin care experiences to push the boundaries of efficacy, safety, and sustainability. Not only efficacy, but safety is key to optimal biohacking and the NeoGenesis technologies, including our S2RM®-core technology, have extensive, peer-reviewed safety studies backing it (Maguire and Friedman, 2020).
With the technologies developed by Dr. Greg Maguire, the products formulated by Dr. Greg Maguire, Dr. Maguire’s patented S2RM technology produced by the NeoGenesis labs led by Linda Green, who has 30 years’ experience as a biotechnologist, lab-director at the University of Florida, and all of our products made in the NeoGenesis laboratories under the direction of Kevin Wiener, a science-grad from the University of California, Santa Cruz. NeoGenesis uses Just-In-Time manufacturing of our ingredients and products to bring the market the freshest, most innovative, and most powerful, efficacious products available.
Whether it’s skin-identical molecules to those produced in the skin by multiple skin stem cell types (S2RM and S3RM technology), the lipids produced in the skin (Triple Lipid Technology), or the dietary botanical-derived ingredients that are brought to the skin through the blood supply (Vibrant C Serum and Skin Restore Serum Vitamin A), NeoGenesis provides the full spectrum of ingredients needed to return the skin to a healthy state and optimize skin longevity.
References
Maguire G. (2013) Stem cell therapy without the cells. Commun Integr Biol. 6(6):e26631.
Maguire G. (2014) Systems biology approach to developing “systems therapeutics”. ACS Med Chem Lett. 2014 Mar 6;5(5):453-5
Maguire G (2018) Adult Stem Cell Released Molecules: A Paradigm Shift to Systems Therapeutics” (Nova Science Publishers, 2018).
Maguire G (2020) Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Amazon Press.
Maguire G, Friedman P. (2020) The safety of a therapeutic product composed of a combination of stem cell released molecules from adipose mesenchymal stem cells and fibroblasts. Future Sci OA. 6(7):FSO592.
Maguire M, Maguire G. (2017) The role of microbiota, and probiotics and prebiotics in skin health. Arch Dermatol Res. 309(6):411-421.
Maguire M, Maguire G. (2019) Gut dysbiosis, leaky gut, and intestinal epithelial proliferation in neurological disorders: towards the development of a new therapeutic using amino acids, prebiotics, probiotics, and postbiotics. Rev Neurosci. 30(2):179-201.
Using GLP-1 agonist drugs has a number of detrimental consequences to human skin, including inhibiting the proliferation, differentiation, and metabolic acitivty of human adipose mesenchymal stem cells (ADSCs). To restore ADSC activity and mimic their activity in the skin, NeoGenesis Recovery, containing the molecules secreted from metaboloically active ADSCs, should be applied to the face to prevent and remediate the negative consequnces of GLP-1 agonists on the skin and its ADSCs.
“Ozempic face” and facial aging have been observed as side effects in many patients after glucagon like peptide 1 receptor agonists (GLP-1RA) therapy for type 2 diabetes mellitus (T2DM) and obesity. While recent studies have found that GLP-1 agonists help the patient reduce weight, and that they also help people with obesity lower their high blood pressure and reduce their odds of heart attacks or strokes, many people are now using GLP-1 agonists just to lose weight. Some physicians are doling these drugs out like candy and all the person wanting them has to do is go online and a physician will sell you the drug. It’s big business and the drug companies can’t keep up with the demand and as a result are raising their prices. So many people taking these drugs means that many, many people are experiencing the negative side-effects of GLP-1 agonists, including a face so sunken that they become unregonizable.
The rapid weight loss observed with GLP-1RA has been implicated in facial aging. However, recent evidence suggests further pathophysiological mechanisms for this side effect beyond just weight loss.
For example, GLP-1RAs were shown to significantly and effectively inhibit the in vitro proliferation and adipogenic differentiation of ADSCs within a few days of exposure, while simultaneously enhancing the production of adiponectin (increases insulin sensitivity) and increasing the fatty acid oxidation (Increasing energy) in adipose tissue. The inhibition of mature adipocyte formation was shown to reduce the presence and activity of fibroblasts in regenerating dermis. Further, in ADSCs, glucose uptake was significantly reduced; the absence of glucose in the ADSCs results in a deficiency of adenosine triphosphate (ATP), leading to cellular dysfunction, damage, aging, and apoptosis of precursor cells.
Importantly, human adipose tissue-derived stem cells (ADSC) secretome display various therapeutically relevant effects in regenerative medicine, such as induction of angiogenesis and tissue repair and regeneration. The benefits of ADSC secretome are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in host cells (Silveira et al, 2022); this means the ADSC secretome not only provides benefit to other cells, such as dermal fibroblasts and adipocytes, but also to the ADSCs themselves through autocrine effects.
Also, Wang et al. 2024 reviewed how ADSC-derived exosomes regulate inflammatory signaling within adipose tissue, with distinct cargo compared to mature adipocyte exosomes. ADSC exosomes contain anti-inflammatory miRNAs (miR-21, miR-24, miR-26) that modulate macrophage polarization and cytokine production within adipose tissue.
While there are some clear benefits to the skin in some patients using GLP-1 agonists such as reducing Advanced Glycation Endproducts (AGEs), there are a number of detrimental effects, such as reduced function of ADSCs and fibroblasts, that can be mitigated or prevented by using NeoGenesis Recovery, containing ADSC secretome.
References
Cantini G, Di Franco A, Samavat J, Forti G, Mannucci E, Luconi M. Effect of liraglutide on proliferation and differentiation of human adipose stem cells. Mol Cell Endocrinol. 2015 Feb 15;402:43-50.
Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS. Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes. J Menopausal Med. 2015 Aug;21(2):93-103.
Ridha Z, Sabrina Guillen Fabi, Raheel Zubair, Steven H Dayan, Decoding the Implications of Glucagon-like Peptide-1 Receptor Agonists on Accelerated Facial and Skin Aging, Aesthetic Surgery Journal, Volume 44, Issue 11, November 2024, Pages NP809–NP818,
Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, Meyer R, Birbrair A, Fortuna V. Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS One. 2022 Dec 19;17(12):e0277863
Wang Y, Li Q, Zhou S and Tan P (2024) Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes. Front. Endocrinol. 15:1374715.
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 Sensingand 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.
I list here some of the reasons why I formulate my skin care products using the secretome of adipose mesenchymal stem cells (ADSCs) instead of bone marrow mesenchymal stem cells or umbilical cord mesenchymal stem cells. ADSCs are better at reducing inflammation and setting the innate and adaptive immune systems into a pro-regenerative state, inducing collagen formation, and laying down that collagen in a manner that is anti-fibrotic.This is a small excerpt of my upcomming peer-reviewed publication.
Listing Efficacy of ADSCs Versus BMSCs versus UCMSCsSecretome (Exosomes + Soluble Fraction)
Bone Marrow Mesenchymal Stem Cells (BMSCs), and the molecules they release, prolong and enhance inflammation by increasing survival and function of neutrophils (Casatella et al, 2011; Liang et al, 2024). BMSC secretome also reprograms hematopoietic stem cells to become inflammatory white blood cells (Ng et al, 2023). 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, the M2 type being anti-inflammatory and therefore the BMSCs are promoting more inflammation (Faulknor et al, 2017; Waterman et al, 2010). Thus, 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.
ADSCs have consistently exhibited much greater anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs (Li et al, 2019).
ADSCs have been found to be highly immunomodulating cells, exceeding the suppressive effect of BMSCs by secreting more anti-inflammatory IL-6 and transforming growth factor-β1 (TGF-β1) Ceccarelli et al (2020).
When compared with the BMSCs- and UCSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site in an animal model (Cao et al, 2024).
ADSCs have biological advantages over BMSCs in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory, ant-inflammatory effects (Li et al, 2015).
Differences in cytokine secretion cause ADSCs to have more potent immunomodulatory effects than BMSCs (Melief et al, 2013)
ADSCs are better at preventing fibrosis than BMSCs (Yoshida et al, 2023).
Adipose mesenchymal stem cell secretome is superior to that of BMSCs because it preferentially helps to rebuild the epidermis by stimulating basal keratinocytes (Ademi et al, 2023).
BMSCs express much CTHRC1 protein (Turlo et al, 2023), which may help to promote fibrosis (Liu et al, 2023).
ADSC exosomes contain SIRT1 (Huang et al, 2020) and activate SIRT1 in other cells (Liu et al, 2021) to reduce inflammation, improve mitochondrial function, and reduce senescence.
ADSC exosomes reduce inflammation in endothelial cells (Heo and Kim, 2022).
ADSCs are considered more powerful suppressors of immune response than mesenchymal stem cells (MSCs) derived from different tissue sources, including trabecular bone, bone marrow, dental pulp, and umbilical cord (Ribeiro et al., 2013; Nancarrow-Lei et al., 2017).
ADSCs immunomodulatory effects exceed that of BMSCs (Melief et al., 2013).
ADSCs secrete higher amount of immune suppressive cytokines, such as IL-6 and transforming growth factor-β1 (TGF-β1) than do BMSCs (Soleymaninejadian et al., 2012; Melief et al., 2013; Montespan et al., 2014).
Bochev et al (2008) showed that ADSCs had a stronger ability to inhibit immunoglobulin (Ig) production by B cells than BMSCs.
Ivanova-Todorova E et al (2009) found that Adipose tissue-derived mesenchymal stem cells are more potent suppressors of the adaptive immune response through limiting dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells.
ADSC secretome inhibits LPS-induced proinflammatory cytokines (Li et al, 2018)
Human ADSCs are key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells (Gonzalez-Rey et al, 2010).
ADSC secretome can suppress the activation, proliferation, and function of CD8+ T cells, which are inflammatory killer T cells (Kuca-Warnawin et al, 2020).
ADSC secretome was able to elevate expression of M2 macrophages and modified their cytokine expression to an anti-inflammatory profile (Hu et al, 2016; Zomer et al, 2020)
Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodeling (Wang et al, 2017).
ADSC exosomes reduce inflammation and alleviate keloids by promoting mitochondrial autophagy through the PI3K/AKT/mTOR pathway (Liu et al, 2024).
ADSC exosomes reduce injury through the transfer of mitochondria components to neighboring cells (Xia et al, 2022).
ADSC secretome expedited wound healing and reduced inflammation in an animal model (Ma et al, 2021).
ADSC secretome promotes wound healing without leaving visible scars and was found safe when injected (An et al, 2021).
ADSC secretome has positive effects on granulation tissue formation and vascularization, and helps prevent fibrosis in pressure ulcers (Alexandrushkina et al, 2020).
Human ADSCs secrete functional neprilysin-bound exosomes that can degrade β-amyloid peptide (Aβ) that is found in the skin – cutaneous amyloidosis (Katsuda et al, 2013; Kucheryavykh et al, 2018).
In psoriasis and eczema the secretome from adipose mesenchymal stem cells (ADSCs), can regulate SOCS (suppressor of cytokine signaling) pathways, and modulate JAK pathways to reduce inflammation (Wang et al, 2022; Ko et al, 2023). Further, the secretome from ADSCs increases SOCS3 expression and, thus, the persistent and uninhibited expression of STAT3 by increased SOCS3 effectively ameliorates tissue injury by promoting tissue regeneration and decreasing inflammation and apoptosis (Lee et al, 2016).
ADSC and BMSC secretomes were characterized by the upregulation of proteins linked to ECM structure and organization and proteolytic processes compared to UCSCs, important to active involvement in tissue repair and microenvironment maintenance and suggesting their advantage for tissue-forming applications (Hodgson-Garms et al, 2025), but ADSCs are better at preventing fibrosis and reducing inflammation (Yoshida et al, 2023).
Fu et al (2025) found that hADSC-Exos are more effective in promoting hair follicle development compared to hUCMSC-Exos, and the secretome of ADSCs was more associated with growth processes such as nucleosome function than was the UCMSC secretome (Fu et al, 2025).
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