Tag Archives: Stem cell released molecules

Mechanisms Of Action of NeoGenesis Hair Thickening Serum

Topical application of Hair Thickening Serum (HTS) promotes hair growth by two key means: Providing, 1. Skin and hair follicle endogenous molecules from skin and hair follicle stem cells (Adipose mesenchymal stem cells, fibroblasts, and dermal papillae) that drive and maintain the transition from telogen to anagen, and 2. Botanical ingredients normally derived from healthy diets that support hair growth.

Simple topical application of NeoGenesis Hair Thickening Serum, b.i.d., twice daily.

Let’s look at the hair growth cycle, and some of the many factors affecting hair growth. I’ll then explain some the mechanisms by which HTS drives the hair follicle to the anagen phase.

Figure 1. Schematic of the hair growth cycle and the factors that may influence a transition from anagen to telogen vs. telogen to anagen phase. From Natarelli et al, 2023.

HTS Mechanisms of Action in the Hair Growth Cycle

HTS’ mechanisms of action at the hair follicle are many. Here I consider a simplified summary of some of the pathways that the stem cell released molecules and botanical ingredients activate or inhibit to drive and maintain the follicle’s transition to the anagen phase.

Transition from Anagen to Telogen

Inflammation – An immunoprivileged state in the follicle is needed to drive anagen, and inflammation transitions the follicle to telogen instead (Bertolini et al, 2020). HTS reduces inflammation in the innate and adaptive immune systems by using the secretome from adipose mesenchymal stem cells – both the exosomal fraction and soluble fractions that act synergistically to optimally reduce inflammation (González-Cubero et al, 2022; Mitchell et al, 2019)

Hormone – ADSC secretome inhibits negative effects of DHT on hair growth (Tang et al, 2023; Fu et al, 2025).

Poor Nutrition – HTS contains nutrients to support hair growth. Larix Europaea Wood Extract, containing Dihydroquercetin-glucoside (polyphenol), EGCG (polyphenol catechin), glycine, zinc, Camellia Sinensis Leaf Extract, Santalum Acuminatum Fruit Extract, Citrus Glauca Fruit Extract, Acacia Victoriae Fruit Extract, Trifolium Pratense (Clover) Flower Extract (providing an abundance of polyphenols and antioxidants).

Stress – ADSC secretome mitigates immunological disturbances affecting the hair follicle (HF) and contributing to hair loss. ADSCs are able to suppress lymphocyte proliferation and, inhibit complement activation and dendritic cell differentiation from monocytes and therefore are considered natural immunosuppressants (Salhab et al, 2022).

Transition from Telogen to Anagen

Blood Flow – Secretome of ADSCs promotes angiogenesis and increased blood flow to follicles (Silveira et al, 2022; Zhu et al, 2020)

Direct stimulation of Hair Growth – Exosomes from dermal papillae cells drive hair follicle stem cell proliferation to rebuild hair follicle (Li et al, 2023), while fibroblasts provide many building-block proteins need to reconstruct the follicle architecture as it transitions from telogen to anagen (Suh et al, 2023).

Increased Local Growth factors – Fibroblasts (Lin et al, 2015), ADSCs (Won et al, 2017), and dermal papillae (HU et al, 2020) secretome all provide necessary growth factors to induce transition to anagen

References

Bertolini M et al (2020) Hair follicle immune privilege and its collapse in alopecia areata. Exp Dermatol. 29: 703–725.

Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17(3): 102088

Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17(3): 102088 [PMID: 40160691 DOI: 10.4252/wjsc.v17.i3.102088]

González-Cubero, E et al (2022) María L. González-Fernández, Elias R. Olivera, Vega Villar-Suárez,Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain,The Spine Journal,Volume 22, Issue 7,2022, Pages 1222-1234

Li J, Zhao B, Yao S, Dai Y, Zhang X, Yang N, Bao Z, Cai J, Chen Y, Wu X. Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1. Int J Mol Sci. 2023 Feb 16;24(4):3961.

Lin WH, Xiang LJ, Shi HX, Zhang J, Jiang LP, Cai PT, Lin ZL, Lin BB, Huang Y, Zhang HL, Fu XB, Guo DJ, Li XK, Wang XJ, Xiao J. Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice. Biomed Res Int. 2015;2015:730139.

Mitchell R et al (2019) Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins. Stem Cell Res Ther. 10(1):116.

Natarelli N, Gahoonia N, Sivamani RK (2023) Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss. J Clin Med. 2023 Jan 23;12(3):893.

Salhab O, Khayat L, Alaaeddine N (2022) Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review. J Biomed Sci. 2022 Oct 5;29(1):77.

Shiqi Hu et al. (2020) Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling.Sci. Adv.6,eaba1685(2020).

Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, et al. (2022) Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS ONE 17(12): e0277863.

Suh SB, Ahn KJ, Kim EJ, Suh JY, Cho SB. (2023) Proteomic Identification and Quantification of Secretory Proteins in Human Dermal Fibroblast-Conditioned Medium for Wound Repair and Hair Regeneration. Clin Cosmet Investig Dermatol. 2023;16:1145-1157

Tang, Xin, Cao, Cuixiang, Liang, Yunxiao, Han, Le, Tu, Bin, Yu, Miao, Wan, Miaojian, Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/β-Catenin Pathway, Stem Cells International, 2023, 5548112, 20 pages, 2023.

Won CH et al (2017) The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors. Curr Stem Cell Res Ther. 2017;12(7):535-543

Zhu, D., Johnson, T.K., Wang, Y. et al. (2020) Macrophage M2 polarization induced by exosomes from adipose-derived stem cells contributes to the exosomal proangiogenic effect on mouse ischemic hindlimb. Stem Cell Res Ther 11, 162.

Eczema: Natural Aryl Hydrocarbon Receptor Activation -Another Pathway Through Which Adipose Mesenchymal Stem Cell Secretome Reduces Inflammation

Activation of the aryl hydrocarbon receptor (AhR) through its natural ligands, has been found to reduce skin inflammation, reduce oxidative stress, and upregulate skin barrier protein expression. AhR also inhibits the generation, persistence, and cytokine production of resident memory T cells in the skin. Stem cell released molecules (secretome) from adipose mesenchymal stem cells includes kynurenine, which is an AhR agonist.

The molecules released (secretome) from adipose mesenchymal stem cells (ADSCs) are diverse (Maguire, 2013) and and have many immunotherapeutic actions. Recent studies provide evidence that one mechanism by which the secretome of ADSCs act is through their agonist activities at Aryl hydrocarbon receptors (AhR). Such AhR agonist activity is highly therapeutic to eczema (Eichenfield et al, 2023).

The aryl hydrocarbon receptor (AhR) is expressed in various tissues characterized by a rapid growth rate, including human skin. Kynurenic acid, a product of tryptophan metabolism enzymatically formed from kynurenine, is a natural ligand for AhR. However, AhR is a promiscuous receptor, binding many unnatural ligands such as environmental toxins. This is important, because if the AhR is activated by unnatural ligands, such as air pollution (PM2.5 for example), ill effects can result. The soluble factors (kynurenine and downstream metabolites) generated by IDO (Indoleamine 2,3-dioxygenase) can bind and activate the aryl hydrocarbon receptor to promote Treg cell differentiation and the induction of dendritic cells expressing an immunosuppressive phenotype. Further, in a dose-dependent response, kynurenine upregulates the expression of immunosuppressive genes, such as TGFB1 and IDO1.

Mechanistically, ADSCs release kynurenine, which is a tryptophan metabolite catalyzed by IDO, to activate the aryl hydrocarbon receptor and enhance its downstream target NFE2L2 in macrophages. NFE2L2-encoded NRF2 not only functions as a master regulator of antioxidant defense but also represses the expression of inflammatory genes. As expected, NRF2 upregulation in macrophages was inhibited by inhibiting IDO and 1-methyltryptophan (1-MT), and the anti-inflammatory effect of ADSCs on macrophages was blocked when NRF2 expression in macrophages was silenced. Kynurenic acid, another IDO-derived metabolite that shares the same aryl hydrocarbon receptor as kynurenine, can promote TNF-α-stimulated gene-6 (TSG-6) expression, which is also released from ADSCs, and alleviate neutrophil infiltration of tissues (Wang et al, 2018).

In summary, the secretome from ADSCs contains a number of molecules (IDO, kynurenine, kynurenic acid) that naturally activate aryl hydrocarbon receptors to reduce inflammation in the skin, and provide long term therapeutic benefit to skin diseases such as Eczema and Psoriasis.

Molecules Released from Human Adipose Derived Mesenchymal Stem Cells and Fibroblasts Promote Epidermal Barrier Repair

The S2RM technology that I developed is based on the molecules released from skin derived adipose mesenchymal stem cells (hASCs) and fibroblasts (HNDF). This combination of many molecules has many benefits to the skin. In this blog, I focus on the benefits of these molecules in helping to repair epidermal barrier function.

A number of diseases and conditions of the skin involve epidermal barrier dysfunction. For example, eczema is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation of the skin. Our previous work has found that S2RM attenuates the symptoms of eczema, including atopic dermatitis (AD). Studies of the mechanisms of action of the molecules present in S2RM suggest that these molecules effectively restore epidermal barrier functions in AD by facilitating the synthesis of ceramides, and creating a thicker epidermis.

hASCs as well as human dermal fibroblasts (HNDF) have a positive impact on keratinocytes proliferation, stemness maintenance, and adhesiveness to membranes via paracrine involvement when co-cultured using the collagen. This means the keratinocytes, largely responsible for building the epidermal barrier, are maintained in a younger and healthier state by the stem cells (hASCs and HNDF) that are releasing molecules into the epidermis from their location in the dermis.

These functions, along with the many other functions of the hASCs and HNDF including modulating immune function into an anti-inflammatory, pro-repair state, important to all epithelial tissues, are critical to good skin health.