Science

NeoGenesis, Inc. has discovered a new core adult stem cell technology, S2RM® Technology, that is used to develop a new class of therapeutic, called “systems therapeutics”  (Maguire, 2014), whereby multiple molecules from two or more adult stem cell types are used to target multiple pathways underling the particular indication to be treated. Our technology is used to formulate the most advanced skin and hair care products on the market today.

Harnessing the power of SRM (stem cell released molecules) from two or more adult stems, hence the term S2RM® Technology, the core technology has been formulated in a number of ways to develop products for skin care and hair care. Skin products have been developed that help the skin become healthier and therefore more beautiful. And, using a different formulation of the core S2RM® technology for fine and thinning hair, simple topical application of S2RM® can lead to thicker and more manageable hair.

Let’s look at this S2RM® technology more closely. Our technology is based upon decades of laboratory and clinical research by Dr. Greg Maguire at the University of California beginning in 1985 at Berkeley with his biophysical, systems studies of the brain, then beginning in 1995 at UC San Diego where he began to work with adult stem cells. Prior to Maguire’s work, many studies had shown that stem cells could replicate themselves and then become almost any type of mature cell in the human body. Maguire’s colleague, Professor Gage at UCSD, showed for the first time that neurogenesis through adult stem cells was occurring in the brain. i.e. new neurons were being produced in the adult brain (Gage et al, 1995). Early studies in Maguire’s lab demonstrated that adult stem cells injected into the brain were inducing their positive effects more through the release of molecules than through their power to differentiate, i.e. transform themselves into new mature tissue. Much work over the years by many prestigious laboratories has shown that stem cell function, and hence the number and quality of the molecules released by the stem cells, declines as we age (Oh et al, 2014). Thus our ability to maintain and heal ourselves declines as we age because of the decline in stem cell function and their reduced ability to produce the SRM. If the molecules (SRM) could be restored to their normal levels in the aged tissue, then the ability of the tissue to maintain and heal itself would be restored to that of the younger,  healthier person.

The NeoGenesis technology has harnessed the healing power of the molecules from adult stem cells to promote healthy tissues.  Having helped to discover that much of the healing power of adult stem (Maguire, 2014B) cells arises from their release of growth factors, cytokines, proteasomes, microRNA, antioxidants, chaperone proteins (Maguire, 2013), all of which are packaged in a naturally produced smart nanosphere by the stem cell itself, called the exosome (Maguire et al, 2013),  NeoGenesis products mimic and stimulate the natural healing process of tissues by restoring to aged, damaged or diseased tissue all of the aforementioned molecules normally found in young, healthy tissue (Maguire and Friedman, 2015). Aging, damaged tissue that has lost many of these molecules can be rescued by adding these molecules back to the skin through topical application of the S2RM®.

Unlike any other company, our patent-pending technology uses the correct combination of adult stem cell types relevant to that particular tissue, stimulates those adult stem cells in state dependent conditions using cell culture processes that reflect the latest scientific knowledge, and harnesses the fully formed molecules for our formulations. Other companies may use genetically modified cells that have genetic and epigenetic reprogramming errors, and use less advanced and less expensive processes to harness an incomplete set of molecules that are not fully formed (for more information see Figure 3 in Maguire et al, 2013).

At NeoGenesis we use the full complement of molecules (S2RM®), all of which are fully formed. This S2RM® technology is natural healing in its truest sense, and a systems therapeutics approach.  The “systems therapeutics” approach means that S2RM® targets many pathways, instead of the traditional reductionist approach of one molecule targeting one pathway. Because all of the molecules are packaged into exosomes, the full complement of molecules are delivered together to the target tissue at the same time and in the same space. Emergent, systems level effects are the result, leading to greater safety and efficacy (Maguire, 2016). Through powerful mimicry and stimulation of the natural healing processes found in human tissue and skin, NeoGenesis’ products achieve superior results, in the immediate and long term, and without side-effects. We simply add back to the aged skin what was once there in young, healthy skin.

The power of S2RM® technology means that homeostasis at the molecular, cellular, and tissue levels can be restored to aged tissue that exists in a state of chronic para-inflammation, thus eliminating the chronic inflammation (Maguire and Smith, 2016). Moreover, new studies in humans demonstrate that  many  age-related metabolic changes may not be inevitable (Chee et al, 2016), meaning that there is much we can do to prevent or mitigate many components of the aging process. The metabolic study reinforces the importance of lifestyle, and particularly physical activity across the life span. NeoGenesis provides one of the means to help prevent metabolic aging of the skin through homeostatic renormalization. Homeostasis is restored by providing the latest stem cell science to the development of skin and hair care products, returning to your body those molecules, 20,000 proteins in only one of many exosomes (Maguire, 2016), that were present in your skin when you were young and healthy. The exosome not only protects and delivers the molecules to the skin’s layers, but also delivers all of the molecules together in space and time so that the molecules act together as a collective, yielding superior efficacy (Maguire, 2014; 2016).

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“Recovery” for Wounds and Traumatized Skin

The process of wound healing is a dynamic series of events involving inflammation, proliferation, maturation, and remodeling. Once the skin is wounded, a cascade of biological processes starts in order to restore the normal tissue anatomy and assure wound closure (Bielefeld et al, 2013). If the healing process is delayed or it fails, a state of pathologic inflammation is established, resulting in chronic wounds. Impaired healing is often associated with ischemia, diabetes mellitus, tumor, venous and pressure ulcers, severe infections, and it can be the cause of reduced quality of life, disability, and even death (Gurtner et al, 2008).

The increased incidence of cancer, eczema, psoriasis, has pointed out the importance to develop new strategies for the effective management of these indications.

For example, in diabetes, there is a delayed influx of inflammatory cells into the wound site initially, but when inflammatory conditions become established, inflammatory cells prevent the deposition of matrix components and remodeling. Recent studies suggest that the ‘receptor for advanced glycation end-products’ (RAGE) is involved in this sustained inflammatory response. Indeed, there is enhanced expression of RAGE in slow-healing wounds in diabetic mice. Thus, in diabetes the skin resides in a continual state of homeostatic disruption, unable to repair wounds. Recovery in this case restores homeostasis of the diabetic skin, and will do the same for other chronic and traumatized skin conditions.

Stem cells in the skin maintain and restore homeostasis through many actions, including their contribution to the generation of well-vascularized granulation tissue, promoting reepithelialization, and attenuating scar formation by several mechanisms, including modulation of the inflammatory environment, enhancement of angiogenesis, promotion of the migration of keratinocytes, and recruitment of other host cells. Thus, the therapeutic application of stem cells has been shown to enhance wound healing and reduce scar formation, doing so through the release of many molecules (Liu et al, 2014).

Our approach at NeoGenesis uses the complete set of molecules released from stem cells known to be involved in scarless wound healing in the skin. Recovery uses a combination of SRM molecules from several stem cell types, all naturally packaged into exosomes that are released from the stem cell types. Included in the ingredients are a number of molecules native to the skin, and helpful in the skin’s maintenance and repair. These include urea, glycerin, hyaluronic acid, and collagen, whose actions are described below.

Urea – Urea is an endogenous metabolite, known to enhance stratum corneum hydration.  Urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. Recent studies show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with therapeutic value to a number of skin diseases and traumatized skin (Grether-Beck et al, 2014).

Glycerin – Aquaporins, the so-called water channels of the skin, form tetramers in the cell membrane, with each monomer acting as a channel. Interestingly, one of the tetramers is a channel called aquaporin 3, which is expressed in skin cells. Aquaporin 3, called an aquaglyceroporin, transports small neutral molecules such as glycerol along with the water to the inside of the cell. Studies show that skin lacking either the aquaporin3 channel, or devoid of glycerol, exhibit dryness and flaking, and impaired healing (Qin et al, 2011).

Hyaluronic Acid – A major component of the extracellular matrix (ECM), hyaluronic acid contributes significantly to cell proliferation and migration. Hyaluronic acid (HA) is a polysaccharide that belongs to the glycosaminoglycan family and consists of a basic unit of two sugars, glucuronic acid and N-acetyl-glucosamine. Many studies have shown that the topical application of HA is beneficial to healing many types of wounds, including trauma, burns, and diabetic ulcers (Neuman et al, 2015).

Collagen – Collagen is the major protein of the extracellular matrix (ECM), comprising 25% of the total protein in the body and 70% to 80% of skin (dry weight). Wounds, especially chronic wounds exhibit an elevated level of matrix metalloproteinases (MMPs). Elevated levels of MMPs not only degrade nonviable collagen but also viable collagen. In addition, fibroblasts in a wound may not secrete sufficient levels of MMP inhibitors (TIMPs) to control the degrading activity of MMPs. This disruption of homeostasis may prevent the formation of the scaffold needed for cell migration and ultimately prevent the reformation of the extracellular matrix (ECM) and granulation tissue. Collagen based wound dressings are uniquely suited to address the issue of elevated levels of MMPs by acting as a ‘sacrificial substrate’ in the wound. Thus, the collagen in the dressing acts as a substrate for the over activity of the MMPs. Further, collagen breakdown products are chemotactic for a variety of cell types required for the formation of granulation tissue, and have the ability to absorb wound exudates and maintain a moist wound environment (Chattopadhyay  and Raines , 2014).

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Ongoing Maintenance and Improvement

In addition to the many conditions Recovery can assist on, NeoGenesis has a number of additional products that are perfect for ongoing maintenance and improvement of the general health of the skin. In additional to the base S2RM®, there are a number of other ingredients that provide the skin with the nutrition to remind itself of it did during its youthful stage.

Hair Science

The skin constantly renews itself throughout adult life (I thought it renews itself at a slower rate as an adult per above), and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration. Mature epidermis is a stratified squamous epithelium whose outermost layer is the skin surface. Only the innermost (basal) layer is mitotically active. The basal layer produces, secretes, and assembles an extracellular matrix (ECM), which constitutes much of the underlying basement membrane that separates the epidermis from the dermis. During activation of the hair follicle, the intradermal adipocyte layer greatly increases the skin’s thickness, and is involved in directing the cycling of hair growth. The hair follicle is an integral component of the skin.  As such, not only will the various stem cell types within the follicle, including those in the bulge region of the follicle, contribute to hair growth (Blanpain et al, 2004), but also the stem cells in the surrounding skin will contribute to hair growth through the release of a number of molecules, including PDGF (Fest et al, 2011).

The NeoGenesis S2RM® strategy for hair growth recognizes the complex mixture of molecules secreted by multiple stem cell types to be a “systems therapeutic,” which will closely mimic the collective actions of the multiple stem cell types in their native state in the human body. S2RM® consists of methods for culturing adult stem cells and progenitor cells in a proprietary, patented (us?), manner, and the “secretome” created by these cells is harvested, purified, and formulated into a topical for treating thinning hair. Specifically, no living cells are present in the formula, only the molecular secretome. The selection of specific stem cell types and culturing conditions leads to the development of a formula specifically suited for the scalp and hair follicle. In this manner, not only is the hair follicle reconditioned with the S2RM® molecules, but the surrounding skin and adipocyte lineage stem cells contained within are restored to a state of normal homeostasis to facilitate hair growth.

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References

  1. Maguire, G. (2014) Systems Biology Approach To Developing “Systems Therapeutics.” American Chemical Society Medicinal Chemistry Letters, 5 (5), pp 453–455.

 

  1. Gage FH, Coates PW, Palmer TD, Kuhn HG, Fisher LJ, Suhonen JO, Peterson DA, Suhr ST, Ray J (1995) Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci USA 92:11879–11883.

 

  1. Juhyun Oh, Yang David Lee & Amy J Wagers (2014) Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nature Medicine 20, 870–880

 

  1. Maguire, G (2014) Maturing From Embryonic To Adult Policy On Stem Cell Therapeutics. American Chemical Society Medicinal Chemistry Letter. http://pubs.acs.org/doi/ipdf/10.1021/ml500396z

 

  1. Maguire, G. (2013) Stem cell therapy without the cells. Comm. & Integrative Biol. V 6. 6. 10.4161/cib.26631.

 

  1. Maguire, G. et al (2013) Stem Cell Released Molecules and Exosomes in Tissue Engineering. Procedia Engineering Volume 59, 2013, Pages 270–278

http://www.sciencedirect.com/science/article/pii/S1877705813010357

 

  1. Maguire, G. and Friedman, P. (2015) Systems biology approach to developing S2RM®-based “systems therapeutics” and naturally induced pluripotent stem cells. World J Stem Cells May 26; 7(4): 745-756

 

  1. Maguire, G. and Smith, D. (2016) Systems Therapeutics To Restore Molecular, Cellular, and Tissue Homeostasis. In Preparation.

 

  1. Chee C, et al., (2016) The relative contribution of intramyocellular lipid to whole body fat oxidation is reduced with age, but subsarcolemmal lipid accumulation and insulin resistance are only associated with overweight individuals. Diabetes 10.2337/db15-1383.

 

  1. Maguire, G. (2016) Exosomes: smart nanospheres for drug delivery naturally produced by stem cells. In: Fabrication and Self Assembly of Nanobiomaterials. DOI: http://dx.doi.org/10.1016/B978-0-323-41533-0.00007-6, Elsevier, In Press.

 

  1. Bielefeld K. A., Amini-Nik S., Alman B. A. (2013). Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol. Life Sci. 70, 2059–2081.10.1007/s00018-012-1152-9

 

  1. Gurtner G. C., Werner S., Barrandon Y., Longaker M. T. (2008). Wound repair and regeneration.Nature 453, 314–321.10.1038/nature07039

 

  1. Liu S., Jiang L., Li H., et al (2014) Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. Journal of Investigative Dermatology.2014;134(10):2648–2657. doi: 10.1038/jid.2014.169

 

  1. Grether-Beck S et al (2012) Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression. J Invest Dermatol. 2012 Jun; 132(6): 1561–1572.

 

  1. Qin H, Zheng X, Zhong X, Shetty AK, Elias PM, Bollag WB. (2011) Aquaporin-3 in keratinocytes and skin: its role and interaction with phospholipase D2. Arch Biochem Biophys. 15;508(2):138-43. doi: 10.1016/j.abb.2011.01.014.

 

  1. Neuman MG, Nanau RM, Oruña-Sanchez L, Coto G. (2015) Hyaluronic acid and wound healing. J Pharm Pharm Sci. 2015;18(1):53-60.

 

  1. Chattopadhyay S and Raines RT (2014) Review collagen-based biomaterials for wound healing. 101: 821–833

 

  1. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. 2004;118:635–48.

 

  1. Fest E et al (2011) Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 146: 761-771.