Tag Archives: neogenesis

Cholesterol in Skin Care

Cholesterol has a negative image among many people given the unhealthy nature of dietary cholesterol. But cholesterol is made by all of our cells, and it is an important component in the skin’s barrier. Let’s quickly look at why cholesterol is successfully used in skin care products.

As the outermost layer of the epidermis, the stratum corneum serves as an important barrier. It is composed of terminally differentiated (fully matured cells), anucleated corneocytes that are derived from keratinocytes, that reside within a lipid matrix. Together, the corneocytes and lipid matrix comprise the “bricks and mortar” structure of the stratum corneum. When combined with ceramides and free fatty acids, cholesterol forms the lipid mortar between the dead corneocytes, forming a water-impermeable barrier that prevents evaporative water loss. This structure, along with other structures such as tight junctions in the epidermis, create a barrier to external insults from pathogens, allergens, and toxins. Cholesterol reaches its highest concentration in the granular layer of the epidermis, just under the stratum corneum.

Cholesterol used in topical products is usually of vegetable origin, primarily derived from squalene. It is safe and effective (when used with free fatty acids and ceramide) as a topically applied product. That is, complete mixtures of ceramide, free fatty acid, and cholesterol facilitate normal barrier function when applied topically. However, incomplete mixtures of these lipids produce abnormal lamellar bodies, the critical organelles that regulate the formation and maintenance of the skin barrier. This leads to an abnormal stratum corneum. In other words, unless you use the complete mixture of lipids; ceramide, cholesterol, and free fatty acids, the barrier function of the stratum corneum will not be optimal. This is why I formulated Neogenesis’ Barrier Renewal Cream to contain the complete set of lipids, including cholesterol, ceramide, and free fatty acids, necessary for optimally building the stratum corneum.

Many people ask, what are these three lipids; cholesterol, ceramide and free fatty acids?

Lipids are fatty, waxy, or oily compounds that are soluble in organic solvents and insoluble in polar solvents such as water. Lipids include:

  • Fats and oils (triglycerides)
  • Phospholipids
  • Waxes
  • Steroids

Lipids that are important to our discussion of skin and human cells include fats and oils (triglycerides or triacyglycerols), fatty acids, phospholipids, and cholesterol. Cholesterol and plant sterols, such as sitosterol, are high-molecular-weight alcohols with a characteristic cyclic nucleus. Fatty acids generally consist of a straight alkyl chain, terminating with a carboxyl group. Ceramides belong to the sphingolipids. Their structure consists of a hydrocarbon chain termed long-chain base, such as sphingosine or phytosphingosine. One fatty acid is linked to the ceramide. In this case, the fatty acid is not “free,” rather it is a component of the ceramide. The free fatty acids are not linked to the ceramide.

The bottom line: The biochemistry of lipids in the body, including the skin, is complex. Just remember the three lipid types that are critical to building normal barrier function, namely, cholesterol, ceramide, and free fatty acids. If you want to delve into the complexity of lipid biochemistry in the skin, a set of excellent research and review papers are found here.

Glycation: What Is It, and How Do We Prevent It?

There’s a big difference between glycation and glycosylation. Glycation is unhealthy, glycosylation is predominantly beneficial.

Glycosylation refers to an enzyme-mediated modification that alters protein function, for example, extending their life span by protecting against denaturation or proteolytic degradation. Glycosylation can also enhance a protein’s interactions with other proteins. By contrast, glycation refers to a monosaccharide (usually glucose) attaching nonenzymatically to the amino group of a protein. In other words, the enzymatic cross-linking of carbohydrates to other organic molecules, such as proteins, is called glycosylation and is an important post-translational modifications of proteins, essential for human cell signaling and metabolism. Glycation is different than glycosylation. Less commonly known is the non-enzymatic and less specific reaction called the Maillard reaction, after its discoverer Louis-Camille Maillard. This is the reaction that underlies the browning of bread. The Maillard reaction takes place in multiple steps, leading to the irreversible formation of advanced glycation end products (AGEs). In the early steps of the reaction, the sugars can react irreversibly with amino acid residues of peptides or proteins to form protein adducts or protein crosslinks. Initially this step of glycation affects the interactions of collagen with cells and extracellular matrix components. However, the most damaging effects of glycation are caused by the formation of glucose-mediated intermolecular cross-links. The cross-linking decreases the critical flexibility and permeability of the tissues and reduces cellular turnover. Advanced glycation end products form and bind to long-lived proteins in the skin, cross-linking them, damaging their structure, deforming their fibers. Many proteins in the skin, including collagen, can be long lived. That is, these long lived proteins don’t turnover for years, sometimes decades. As such, they are susceptible to damage, including through glycation. This glycation of collagen in the skin, noticeable as browning skin, likely means glycation of the collagen is happening in other parts of the body, including the cardiovascular system.

In the last step, when oxidation is involved, the products are called advanced glycation end products (AGEs). AGEs are formed through four pathways: (1) the Maillard reaction, (2) sugars auto-oxidation pathway, (3) lipid peroxidation pathway, and (4) polyols pathway. Glucose is converted into fructose via the polyol pathway (based on aldo-keto reductase enzymes), which accelerates the production of AGEs. The formation of AGEs is a slow process that occurs physiologically in vivo, with higher accumulation of AGEs in tissues with slow renewal rates, such as the skin’s long lived proteins. AGE levels are increased in patients due to increased production, but they are also increased due to impaired excretion. In conditions such as metabolic and oxidative stress, AGE accumulates more rapidly. New, non-invasive assessment techniques of AGE are now available. The measurement is made using skin autofluorescence.

Not only is the skin autofluorescence (SAF) a measure of AGE in the skin, but the value determined in the skin is highly correlated with that in other parts of the body. That is, the measurement of AGE accumulation in the skin can serve as a biomarker for disease states other than those in the skin, including cardiovascular disease and diabetes mellitus. Chronic kidney disease has also been recently shown to correlate with SAF. As I have said previously, the health of the skin is an important biomarker for the health of many other organs in the body.

Not surprisingly, an environmental factor that is likely to have a profound effects on AGE accumulation is diet. Studies have shown that breastfed infants, consuming few AGEs, had lower SAF intensities than formula-fed infants, a diet rich in AGEs. Meat consumption is also associated with higher AGEs, where lower SAF values have been observed for vegetarians in hemodialysis patients.

In addition to environmental factors, herditary factors are likely to contribute a small amount to the observed AGE phenotypes as measured by SAF.  Studies of twin and sibling pairs have implicated heredity as partly responsible for lens and skin fluorescence variations.

So what can we do? Reducing our consumption of sugars and simple carbohydrates is one obvious prophylactic measure. Another is reducing one’s consumption of meat, and eating a diet rich in vegetables. And, because environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury, restriction of dietary AGEs will suppress these effects. This is true in the skin, as well as throughout the body. Further, because metabolic state, and oxidation are important to driving the formation of AGEs, in addition to healthy lifestyle and dietary practices, one can use a course of topically applied skin care products to promote better metabolism, increased anti-oxidative capacity, and a renormalization of the extracellular matrix (ECM) in order to better prevent glycation and the formation of cross-linking and AGEs in the skin. Important to a skin care routine to prevent and remediate AGEs is the inclusion of NeoGenesis’ S2RM technology to prevent and remediate damage to the ECM and to provide a wide variety of antioxidants.

Skin Derived Adipose Mesenchymal Stem Cells and Their Secretome in Wound Healing and Skin Aging

Adipose-derived stem cell secretome has been successfully used for treatment of various diseases, e.g., multiple sclerosis, rheumatoid arthritis, osteoarthritis, fistulae, diabetes mellitus, autoimmunity, and cardiovascular diseases, but also in skin aging, skin diseases, and wound healing. Let’s focus on the skin wound healing and aging.

Skin derived adipose mesenchymal stem cell (AMSC) secretome is a key component in the S2RM technology used by NeoGenesis in many of its skin care products. These mesenchymal stem cells are found in the hypodermis and dermis of intact, normal skin. Secretome is the complete set of molecules released by the AMSCs, the same set of molecules that the AMSCs in the skin normally release to help maintain and heal the skin. Secretome is what we call “stem cell released molecules (SRM)” at NeoGenesis. All the molecules released by the stem cell. And the “2” is present because we use the SRM from two types of skin derived stem cells, hence S2RM. So what we’re using at NeoGenesis is the complete set of all stem cell released molecules from two types of skin-derived stem cells, including the AMSCs. The other stem cell type used in the S2RM are fibroblasts derived from the skin. Fibroblasts are progenitor cells that are distinct from mesenchymal stem cells. Here’s a quick look at why this skin-identical ingredient, S2RM, is so useful in skin care. We’ll focus on the AMSC component of the S2RM. In another post, I’ll describe the many benefits of the fibroblast secretome. The approach we use at NeoGenesis is what I call, “Stem cell therapy without the cells,” a methodology that uses the many molecule types released from skin resident stem cells to renormalize the skin’s physiology.

The skin is physical barrier against physical, chemical, and biological damage. It is normally self-repairing, and protects against dehydration and thermal, pathogenic, chemical, and physical stress. Repairing physical damage in the skin is a dynamic process involving five overlapping stages of homeostasis, inflammation, proliferation, re-epithelization, and fibrosis. In clinical practice, AMSCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated stromal vascular fraction (SVF or cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. AMSCs, as part of the full thickness skin grafts, have been used by physicians in their practices beginning in 1875 when Hungarian-born Scottish-trained surgeon John Reissberg Wolfe first developed the technique.

Let’s explore some of the mechanisms by which AMSCs exert their maintenance and repair of the skin. The mechanisms are complicated, and I’ll give you a glimpse into the many proteins and pathways that underly how AMSCs work in the skin. I’ve published on the immune modulating actions of AMSCs, and those of you interested in those aspects of AMSCs can read the paper as a free, open-access PubMed listed journal article. While the detailed pathways I write about below may not be important to those of you who are not scientists, what’s of value is to recognize the many pathways and many molecules types that are involved in maintaining and healing the skin. Products using one or a few peptides or proteins for example, will have minimal effect in bringing the skin to a healthy physiological state. In contradistinction, products that contain the many molecule types, such as S2RM, needed to maintain and heal the skin, will bring safe and efficacious results.

As part of their secretome, AMSCs secrete four key growth factors that promote re-epithelization: EGF, FGF-2, IGF-1, and TGF-β. These proteins induce the mechanisms underlying tissue repair including cell migration, proliferation, and differentiation as well as angiogenesis, extracellular matrix production, and inflammation resolution. Studies have found that co-treatment of AMSCs and AMSCs secretome increases the proliferation of dermal keratinocytes and fibroblast in the skin, and the maturation of fibroblasts through, at least partially, the upregulation of microRNA. Other studies have found that AMSC secretome prevents flap necrosis (cell death) after skin flap transplantation by increasing proliferation and secretion of IL-6. Another study found that AMSC secretome enhances skin flap recovery by reducing inflammation and apoptosis. AMSC secretome also prolongs the survival of vascularized composite allografts after transplantation by immune modulation, downregulating CD4+ T and Th1 cells and upregulating Tr1 and Treg cells. This paper exemplifies that the use of AMSCs secretome is an important new approach in reconstructive and plastic surgery. This is the all-important regulation of the immune system that is necessary for wound healing as described in my recent paper.

Key to tissue repair is the mitigation of inflammation. In addition to secreted immunomodulatory proteins by AMSCs, it is possible to modulate inflammatory pathways by microRNA in the AMSC secretome. Studies have found that AMSC secretome contains miR-21, which increases migration and proliferation of HaCaT (keratinocytes) cells by enhancing the matrix metalloproteinase 9 (MMP-9) expression in the PI3K/AKT pathway, thereby increasing wound healing. Also, miR-19b from AMSC secretome enhances wound healing by regulating the TGF-β pathway through targeting chemokine C-C motif ligand 1 (CCL1) by modulating the CCL1/TGF-β signaling axis. Delving more into these mechanistic pathways, TGF-β secreted by AMSCs has been found to act synergistically with growth differentiation factor 11 (GDF11) to reverse keratinocytes aging and trigger skin rejuvenation. Enhanced re-epithelialization, collagen remodeling, angiogenesis, and vessel maturation leading to improved wound healing were also found in diabetic mice treated with engineered AMSC secretome containing miR-21-5p. In digging deeper into these pathways, keratinocyte proliferation and migration and accelerated wound healing were induced through the Wnt/β-catenin signaling pathway in vitro, confirming earlier results where AMSC secretome was found to improve wound healing also through the Wnt/β-catenin pathway. AMSC secretome can also be used in alleviating atopic dermatitis.

Studies have found that an in vivo model of atopic dermatitis after AMSC secretome injection exhibited reduced clinical score, decreased level of inflammatory cytokines, serum IgE and blood eosinophil counts and CD86+ and CD206+ cells in skin lesions, as well as diminished infiltration of mast cells. Moreover, it has been shown that levels of inflammatory cytokines such as IL-4, IL-23, and IL-31 were reduced. Recently, Shin et al. found that not only the levels of these cytokines are reduced after AMSC secretome treatment in atopic dermatitis, but also IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP were reduced. The study also demonstrated that AMSC secretome restored expression of genes responsible for lipid metabolism, including ceramides, the cell cycle, a normal inflammatory response, as well as improving the skin barrier.

Furthermore, AMSCs and their secretome can be used in skin rejuvenation and wrinkle reduction, partly by stimulating collagen synthesis and regulating the proliferation and migration of dermal fibroblasts. You can think of wrinkles as a type of wound. Other studies have demonstrated the protective function of AMSCs secretome on dermal fibroblasts and keratinocytes against UVB-induced photoaging. They found reduced skin cellular senescence was observed in the group given AMSC secretome after UVB irradiation. Moreover, treatment with AMSCs secretome improved collagen I, collagen III, elastin, and TIMP-1 expression. AMSC secretome treatment was also able to upregulate the antioxidant response element (ARE), thus preventing and remediating damage to lipids, proteins, and DNA in the skin. 

These examples provide a glimpse into the complexity of maintaining and healing the skin, and exemplify why carefully formulated products that contain a multitude of skin-identical proteins, such as the S2RM in NeoGenesis products, are critical to providing a natural, safe, and efficacious means for skin care.

The Reductionist Pharma Mindset in Start-Up Skincare Companies – Purveyors of Magic Bullets

The recent spate of start-up skincare companies featuring technologies that rely on one one magical ingredient belie the complexities of the skin’s physiology – When will they ever learn about “Systems Therapeutics for Physiological Renormalization”?

Some recent examples of magic bullets being funded by venture capital and brought to the market by their marketing puppets include: the long-available and widely used ingredient called, phytosphingosine; a peptide du jour called OS-01 Peptide; another peptide du jour with the tradename, LIPOXERASE. I could go on, but these are a few examples that popped up on my radar over the weekend. Let’s be clear, the mindset of these private equity funded skin care companies is to develop skin care products in the same manner as drug companies. That mindset is reductionist, meaning that they feature one ingredient as a “cure all.” But making drugs that cure a disease is a bad business model – if it’s cured, the customer goes away and money is lost. The reductionist strategy is why most drugs don’t work, and most have serious negative side-effects. I wrote a book about this. Pharma knows it. Often the key is to develop one ingredient for which a patent can be attained. It doesn’t matter if the patented ingredient really works, it just matters that a patent is in place. Once the patent is granted, no one else can use the ingredient for about 15-20 years. This makes for great marketing hype in the USA. A new patented ingredient will spread like wild fire through the corporate media circles, and having heard the corporate media hype thousands of times over, many will believe the nonsense. These companies will make money, because with private equity behind them, they’ve got the money to hire the Mad Men. Private equity is a huge negative for healthcare. It doesn’t matter that the new patented or “patent-pending” (anyone can say this) product doesn’t work well, media hype will say that it does and people will buy it. Private equity makes money, your skin will whither.

So when will these people learn about “Systems Therapeutics for Physiological Renormalization“? The skin has a very complex physiology. And when you have a skin disease, the changes in physiology are complex. The disease is not about one pathway in the skin changing, and then using one ingredient to fix the pathway. Rather, disease is complex and involves many pathways, and a systems therapeutic that targets multiple pathways underlying the disease is required to significantly ameliorate the disease. That means many molecule types are delivered to the skin to renormalize the physiology, affecting all or many of the pathways underlying the disease, and to bring the skin back to a non-diseased state. This is the approach we use at NeoGenesis, the skincare company that I co-founded. We use a multitude of molecules, most of which are skin-identical, to renormalize the skin’s physiology. Those skin identical ingredients include the S2RM molecules – a collection of many molecule types that are released from adult stem cells derived from human skin. These molecules are an example of endogenous skin identical ingredients, because they are molecules produced by cells in the skin. We also use exogenous skin identical ingredients, such as Vitamin C, A, and E and essential fatty acids, that are derived from a healthy diet. These are all skin identical ingredients because they are normally found in the skin and man evolved to naturally use these ingredients, whether they are made in the skin or acquired through diet. Choosing a myriad of healthy ingredients with which man co-evolved is how I formulate our products at NeoGenesis. It’s not about one magical ingredient, it’s about a collection of healthy ingredients.

“Systems Therapeutic for Physiological Renormalization,” A Paradigm Shift in Skin Care

As Dr. Thomas Kuhn, a former physics professor at Harvard and Berkeley, taught in his book, The Structure of Scientific Revolutions, scientific fields undergo periodic “paradigm shifts” rather than progressing in a linear and continuous way, and that these paradigm shifts lead to new approaches in understanding what scientists would never have considered valid before. Such a paradigm shift is now underway for drugs and therapeutics, specifically for skin care, and has been described as “Systems Therapeutics for Physiological Renormalization.” Until now, the paradigm for drug and therapeutic development has been an ineffective reductionistic approach, where a small molecules was developed to target one pathway in an attempt to remedy the diseases or condition. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, long believed to be the oracle for teaching pharmacology to physicians and other practitioners, taught that “the small molecule had to specifically hit its target, and only its one target.” That is, their misguided approach is to develop a drug or a product that specifically hits one target, and only one target, and that is thought to be the best way for drug or skin care product development. It’s nonsense. This doesn’t work well because all diseases and conditions of the skin involve multiple pathways at multiple levels in the tissue, and therefore multiple molecules, not just one, are required to renormalize the multiple pathways in the diseased tissue to ameliorate the disease or condition.

Examples in skin care of this reductionist approach are to offer products that focus on one antioxidant, namely Vitamin C, as a cure all. You’ll see many products on the market that prominently feature Vitamin C, and only Vitamin C, as their active antioxidant ingredient. Sometimes the product has C and E, and only C and E. Your body’s cells naturally produce many powerful antioxidants, such as melatonin, alpha lipoic acid, superoxide dismutase, and glutathione. The foods you eat supply other antioxidants, such as vitamins C, ergotheoneine, carotenoids, and vitamin E. Many antioxidants, including these and others, naturally work together in the antioxidant cascade. It’s not just about Vitamin C. Too much Vitamin C can actually be oxidative and potentially damaging, and inhibit other normal biochemical pathways in the body. The evidence is not clear about the damaging effects, but too much is suboptimal. Rather, it’s about a combination of different types of antioxidants used together. Just as nature intended. This is clear, you need a wide variety of antioxidants, not just vitamin C. It’s similar to when you eat a wide variety of fruits and vegetables, with all those different colors due to the different kinds antioxidants and other molecules they contain. All of those different molecule types are required to keep us healthy. And many of those colorful molecules will be pumped into the skin from the blood supply, feeding the skin from the inside-out. When formulated properly and applied topically to the skin, most of those molecules can feed the skin from the outside-in.

Most diseases and conditions involve many perturbed pathways, and a product that targets only one of these many pathways is a product doomed to failure or suboptimal therapeutic effect. As an example, such is the case for well over 50% of the FDA-approved drugs on the market today, they don’t work. The drugs that don’t work include many cancer drugs, that are toxic and only cause harm. While this problem has received media attention, the world’s largest lobby, the medical-industrial complex, drowns out these reports by saturating the media with drug propaganda. This way of thinking permeates social media, and many skin care products will tout their favorite ingredient in a reductionist manner. That is, they tout one ingredient as a cure all. EGF products are an example of this nonsense. They promote one growth factor out of hundreds that used in the skin’s biochemical pathways. EGF alone will puff up the face like a balloon, causing depilation (loss of hair). It’s not healthy.

This problem of reductionism only became worse when physicians, such as Francis Collins, ushered in genomic fashionistaism, teaching that the small molecules should not only hit just one target, but that the target should be at the level of the genome. As Dr. Stephen Rappaport, Ph.D. at Berkeley teaches us, over 90% of diseases are caused by our exposome and mutations in the genome are not the underlying cause. Yet, Collins in all of his ignorance, called for genetically sequencing everyone, carrying your genetic sequence on a card that can be read by physicians, such that the physician can then treat you based on the information contained on your “genomics card.” Another physician, Leroy Hood, was quoted as saying, ” your entire genome and medical history will be on a credit card. You just put it in there [a computer] and a physician will instantly know what he’s dealing with.” Besides irrational thought underlying Collin’s call for a “genome card,” fraud was in his calling to make such ignorant claims. Publishing five fraudulent paper on genomics. When found out, Collins said, “the significance and the scope of the fabrication in this circumstance, of which I had not the slightest idea, began to be very apparent.” In other words, Collins had no idea what was going on in his lab, and was attaching his name to “scientific papers” of which he had nothing to do with. This is called “ghostwriting,” where physicians put their names on “scientific papers” yet have had nothing to do with the study. The practice is rampant for practitioners, i.e. physicians. Leading other physicians astray, who control over 95% of biological research spending in the US given that physicians control the National Institutes of Health, Collins would cause biological research in the USA to be highly biased towards looking for diseases in all the wrong places – the genome. This mentality of looking for disease in all the wrong places has hit skin care and the beauty industry. At Neogenesis, I formulate products that are based on the “systems therapeutics for physiological renormalization” approach, where our core technology, S2RM Technology, is compromised of hundreds of proteins native to healthy, young skin, that can be returned to aged and/or damaged skin through simple topical application. And, the molecules in S2RM are used in combination with other skin identical ingredients, such as Vitamin C, Vitamin E, ergotheoneine, carotenoids, SOD, urea, squalane, ceramide, etc, to renormalize the skin’s physiology. It’s a natural, efficacious, and safe approach to skin care. All of the ingredients in the products are carefully chosen to not induce inflammation or an allergic response.

The reductionist and genomic bias continues today and has been taken to such an absurd level that almost every gene studied has been linked to a disease. Further upsetting those who believe that mutations in the genome underlie disease, is that mutations in the genome don’t happen just by chance, but are driven by environmental influences. Basically, one’s health status is not only influenced by your current environment acting at the protein level of your body, but also by what your ancestors experienced in their environments acting on their genetics and epigenetics. So what you do in life, including your diet, directly effects your health and can cause most diseases, but also will have consequences to your children and their children. As such, when what one has experienced in life disrupts their physiology, mostly acting at the protein level of the body, the resulting disease can be treated by renormalizing the physiology. This means, renormalizing the protein (and other molecules such as lipids) content of the afflicted tissues. As Dr. Daniel Nomura, Ph.D,, professor at Berkeley, has written, “Many diseases, including cancer and monogenic diseases, are often caused by specific proteins that are abnormally degraded and lost from the cell.”

As an example of the therapeutic benefit of this “systems therapeutic for physiological renormalization” approach, our group has demonstrated its efficacy in the skin for a number of conditions, including radiation dermatitis in cancer patients. The approach was also shown by Maguire and colleagues to be effective in protecting the nervous system from neurodegenerative diseases in an experimental animal model. The safety of this technology has been demonstrated, and the mechanism of action partially described. The approach has also been discussed in an interview of Dr. Greg Maguire by Dr. Tom Kleyman of the Physiological Society. Dr. Maguire has also recently described in a journal publication, Human Vaccines and Immunotherapeutics, how the “systems therapeutics for physiological renormalization” approach may help to make safer and more efficacious vaccines, helping to better prevent the spread of the disease. I’ll be speaking about this an upcoming talk at the 8th Annual Vaccines Research & Development congress in Nov. 2023. The point here is that this strategy of using a systems therapeutic (many types of molecules) to bring about physiological renormalization (restoring normal protein content, for example) can work for all tissues and for all kinds of diseases and conditions, including those of the skin. Remember, it’s the proteins (plural!), stupid. Not the genome, not just one molecules.

Stay tuned, there is much more to come, including our approach in treating immune and autoimmune conditions, including of the skin, as I began to describe in my 2021 paper.

Prebiotics, Probiotics, and Postbiotics as Part of the NeoGenesis Core Technologies

NeoGenesis is known for its core stem cell released molecules (S2RM) technology. Another core technology, the use of prebiotics, probiotics, and postbiotics is also key to the efficacy of Neogenesis products. These technologies are part of our therapeutic approach, using system therapeutics for physiological renormalization.

I coined the term “postbiotic” a few years ago in a peer-reviewed PubMed listed paper that details how important prebiotics, probiotics, and postbiotics are for human health. As a term that I recently coined, and that has rapidly gained wide popularity, I’d like to emphasize the definition of postbiotic. A postbiotic is a molecule that has been produced by a microorganism that provides benefit to the host, i.e. the person to which the molecule has been applied. Postbiotics can be naturally occurring, such as the butyrate that bacteria on our skin are producing. Butyrate is a short chain fatty acid that quells inflammation in the immune system of the skin. Butyrate can also be produced by bacteria in a laboratory, collected and added to a topical product, and then applied to the skin. This too is a postbiotic. We can describe the first instance, where bacteria on the skin are naturally producing butyrate as an endogenous postbiotic, and the second instance, where bacteria produce butyrate in the lab and then it is applied to the skin, as an exogenous postbiotic. Either way, butyrate on the skin is a postbiotic and providing benefits to the skin.

At Neogenesis, we use a form of butyrate in several of our products, including our probiotic product, MB-1. Yes, MB-1 actually has live bacteria and does not use antimicrobial preservatives that would kill the probiotic. So the MB-1 product has both postbiotics and probiotics. In an upcoming post I’ll tell you about another probiotic product that Neogenesis will be launching specially designed for atopic, inflammatory skin conditions. We also use butyrate in our Eye Serum, Booster, and our Barrier Renewal Cream. It’s a great postbiotic, and dermatologist researchers in Germany have found it to be particularly beneficial for modulating the immune system in atopic and inflammatory skin conditions.

Now for prebiotics. Hyaluronic acid (HA) is a prebiotic, and has been found to upregulate those short chain fatty acids, such as butyrate in the aforementioned paragraph. In this case, bacteria that are part of the body are fermenting HA and producing butyrate, a postbiotic. Hence, in this case HA is a prebiotic because bacteria on our skin are using it to produce butyrate, a beneficial molecules.

Now, for the kicker. HA can also be an exogenous postbiotic. That is, HA can be produced in the laboratory by bacteria, and then collected, packaged into a product, and applied to the skin. That’s a postbiotic, albeit an exogenous postbiotic because it wasn’t produced by bacteria on our skin. So in this case, HA is an exogenous postbiotic, having been produced by bacteria in the lab, but acts as a prebiotic because it is feeding bacteria on our skin that produce a postbiotic. Normally, HA is not a postbiotic in the skin. Rather, normally, HA is produced by our own cells in the skin. Fibroblasts in our skin normally produce the HA. I’ll have more about the microbiota of the skin in future posts, where we’ll learn about the skin’s microbiota in educating the immune system and in helping to maintain the acid mantle and barrier function.

Why Skin-Derived, Adipose Mesenchymal Stem Cell Released Molecules (NeoGenesis) Are Better Than Bone Marrow Mesenchymal Stem Cell Cytokines (AnteAge) for Post-Procedure Healing

What AnteAge Doesn’t Know and Therefore Doesn’t Tell You

Consider 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 damging your skin. In contradistinction, consider the cells used by Neogenesis. The phenotype and stem cell released molecules (also called the secretome) from skin-derived adipose mesenchymal stem cells (AMSCs) are largely unaffected by prolonged hypoxia, not recruiting neutrophils (Kalinina et al, 2015), and the molecules released from AMSCs were found to better induce the effects of the anti-inflammatory M2 macrophage phenotype than the molecules released from BMSCs (Sukho et al, 2018). These results provide strong evidence that the molecules released from AMSC are more beneficial than those from BMSCs to induce appropriate wound healing processes through the shift from a pro-inflammatory state to an anti-inflammatory, pro-healing state.

These pro-inflammatory signals from BMSC cytokines are in addition to their likelihood of containing pro-oncogenic signals that are absent in AMSCs, that I have previously reviewed in multiple, peer-reviewed, National Library of Medicine journal articles (Maguire, 2019; 2021; 2022).

Why does AnteAge use these inflammatory and potentially oncogenic molecules in their products? The first clue comes from who founded the company and was its CEO for years, John Sanderson. A former physician who lost his medical license because of incompetence, repeated incompetence, and sexual misconduct with one of his patients.

Sanderson previously was a family practice physician with an undergraduate medical degree – a bachelor’s degree in medicine. Once Sanderson finished his Canadian undergraduate degree in medicine, once he passed the medical board test in the US, regulations permitted him to use the designation “M.D.” Sanderson frequently finds himself in disputes with other companies, one of which exposed that Sanderson committed domestic violence. He was not trained as a dermatologist and was not board certified. He obviously has little to no understanding of the skin’s powerful immune system, and no idea of how bone marrow mesenchymal stem cells work in the body. Upon losing his medical license, he started a company to do further harm to people by having them use products that induce inflammation and potentially cancer.

Trying to understand why a company would bring a proinflammatory, possibly pro-oncogenic product to the market, I looked closer at the company. Because John Sanderson is not a scientist, and has never listed that he has any scientific publication, only misleading blogs, I wondered how did he come to choose his technology. I discovered that Sanderson had enlisted fellow Canadian, Jonathan Lakey, Ph.D. as his scientific advisor. To no surprise, the man who had lost his medical license because of incompetence had hired a scientist, Jonathan Lakey, who had been fired from his university because of fraud.

A non-profit government organization in Canada fired Jonathan Lakey for the same reason:

Then Jonathan Lakey was charged with fraud and racketeering at one of the companies in which he was an officer:

Jonathan Lakey’s involvement with a number of other companies that are pump and dump schemes has made the news a number of times. Clearly, using a product on your skin from this dynamic fraudster-incompetence duo is a bad choice – they do not have anyone’s well being in mind.

There are other skin care companies led by physicians. I suggest if you’re interested in their products, go to the state medical board website in which they practice, and look at the current status of their medical license. For example, you can search physicians in California here, and in Colorado here. You may be surprised what you find. Simply type in their name, and you’re likely to find disiplinery actions and loss of license.

References

Castella M.A. et al (2011) Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells. 29:1001–1011.

Faulknor R.A. et al (2017) Hypoxia impairs mesenchymal stromal cell-induced macrophage M1 to M2. Technology. 2017;5:81–86. doi: 10.1142/S2339547817500042.

Kalinina N. et al. (2015) Characterization of secretomes provides evidence for adipose-derived mesenchymal stromal cells subtypes. Stem Cell Res. Ther. ;6:221.

Maguire G. Transplanted stem cells survive a long time: do they make you sick? J R Soc Med. 2019 Oct;112(10):412-414.

Maguire G. (2021) Stem cells part of the innate and adaptive immune systems as a therapeutic for Covid-19. Commun Integr Biol. 14(1):186-198.

Maguire G. (2022) Chronic inflammation induced by microneedling and the use of bone marrow stem cell cytokines. J Tissue Viability. 31(4):687-692.

Sukho P et al (2018) Human mesenchymal stromal cell sheets induce macrophages predominantly to an anti-inflammatory phenotype. Stem Cells Dev. 27:922–934.

Waterman R.S. et al (2010) A new mesenchymal stem cell (MSC) paradigm, polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS ONE. 5:e10088.