Conventional and novel stem cell based therapies for androgenic alopecia

Figures & data

Figure 1 Diagram of the HF and factors involved in hair regeneration.

Notes: The HF is composed of different cell types including HFSCs, DPCs, and ECs, among others. HFSCs migrate from the bulge area after activation by growth factors released by DPCs. However, BMP6 and FGF18 from the bulge cells exert autocrine inhibitory effects in HFSC proliferation. Once the HFSCs are closer to DPCs and ECs, they differentiate and proliferate during anagen phase, forming new hair. Activation of Wnt signaling is essential for DPCs to release the factors that promote differentiation and proliferation of HFSCs. DHT interferes with this Wnt signaling and, in this way, inhibits hair growth and promotes hair miniaturization. Effective cell–cell interactions between HFSCs, DPCs, and ECs are essential for hair growth.
Abbreviations: BMP6, bone morphogenetic protein 6; DHT, dihydrotestosterone; DP, dermal papilla; DPCs, dermal papilla cells; ECs, endothelial cells; FGF18, fibroblast growth factor 18; HF, hair follicle; HFSCs, hair follicle stem cells.

Table 1 Prescribed products used for AGA

Prescribed products	Source	Mechanism of action
Finasteride/Dutasteride^Citation9,Citation10	Synthetic (small molecule)	Inhibits type II, 5α-reductase
Latanoprost and Bimatoprost^Citation36,Citation38,Citation39,Citation79,Citation80	Synthetic prostaglandin analog of PGF2α (originally used to decrease ocular pressure in glaucoma)	Activates prostaglandin receptor

Abbreviation: AGA, androgenic alopecia; PGF2α, prostaglandin F2α.

Table 2 Non-prescription products used for AGA and their proposed mechanisms of action

Non-prescription product	Source	Proposed mechanism of action
Minoxidyl (FDA approved)^Citation9	Synthetic (small molecule)	Potassium channel opener and powerful vasodilator used in hypertension
Apple Procyanidin B-2 (extract from apples)^Citation40	Natural (apples and several plants)	Inhibitor of translocation of PKC isozymes in hair epithelial cells
Procerin (saw palmetto extract and other ingredients such as iodine, gotu kola, magnesium, grape seed extract, biotin, niacin, and vitamin B12)^Citation42	Natural (small plant named saw palmetto)	Used to treat benign prostatic hyperplasia. Inhibits type I and II 5α-reductase and blocks DHT production
Provillus (www.provillus.com)	Formulation (Minoxidil 2 or 5%, biotin, Zn, Fe, Mg, Ca, B6 complex)	Contains Minoxidil and more vitamins (similar ingredients to Procerin)
Follicusan (https://www.ulprospector.com/en/na/PersonalCare/Detail/1381/216299/Follicusan-DP)	Natural (milk-based bioactive compound)	Stimulates cellular functioning in the scalp and hair follicle. Stimulates dermal papilla cells. Improve hair density and thickness
Musol 20 (http://www.cosmeticingredients.co.uk/Ingredient/musol-20-pf)	Natural (yeast extract, mucoprotein)	Physically deposited as a protective covering to create thicker hair
Capixyl (http://lucasmeyercosmetics.com/en/products/product.php?id=6)	Synthetic and natural (four amino acids biomimetic peptide with red clover extract; rich in biochanin A [antioxidant])	Inhibitor of 5α-reductase, improves ECM proteins; it reduces inflammation
EMortal Pep (http://www.revagain.co.kr/goods/catalog?code=0002)	Synthetic and natural	Blocks upregulation of TGF-β1 induced by DHT. Activates dermal papilla cells
Planoxia-RG (https://www.ulprospector.com/en/na/PersonalCare/Detail/5314/195870/PLANOXIA-RG)	Natural	Promotes transition from telogen phase to anagen phase
Tricholastyl (http://dir.cosmeticsandtoiletries.com/detail/tradeName.html?id=17820)	Natural (water, mannitol, Pterocarpus marsupium bark extract, disodium succinate, glutamic acid)	Antiglycation activity. In this way, it restores the hair growth cycle
Keramino-25 (http://www.lonza.com/productsservices/consumercare/personalcare/proteins/animal-proteins/keramino-25.aspx)	Synthetic	Increases the strength of the hair (because of its great penetration)
Seveov (http://www.naturex.asia/uk_1/markets/personal-care/natbeautytm/seveov.html)	Natural (maca root extract)	It protects the hair bulb and shaft. It stimulates cell division in the hair shaft and bulb
Hairomega (http://thehairlossreview.com/hairomega_review.html/)	Natural (formulation that contains [200 mg] saw palmetto and [300 mg] β-sitosterol as the main ingredients)	Inhibits 5α-reductase and formation of DHT
Green tea (Epigallocatechin gallate)^Citation43,Citation91	Natural (polyphenol antioxidant)	Inhibits 5α-reductase and formation of DHT
Nioxin (formulation of Coenzyme Q10 and other coenzymes) http://www.nioxin.com/en-US?&utm_source=google&utm_medium=cpc&utm_term=nioxin&utm_campaign=Nioxin_Search_Brand+Awareness&utm_content=sMPLlfxxa|dc_45273195217_e_nioxin&gclid=CJSy3JbH0cgCFY17fgodMTIDK Q	Synthetic	Inhibits 5α-reductase and formation of DHT
Alfatradiol (17α-estradiol)^Citation44	Synthetic (small molecule)	Inhibits type II 5α-reductase
Quercetin^Citation84	Natural (flavonoid found in several non-citrus fruits, vegetables, leaves, and grains)	Inhibits PGD2

Abbreviations: AGA, androgenic alopecia; DHT, dihydrotestosterone; ECM, extracellular matrix; FDA, US Food and Drug Administration; PGD2, prostaglandin D2; PKC, protein kinase C; TGF-β1, transforming growth factor β1.

Table 3 Stem cell factors and small molecules that promote hair growth and their mechanisms of action

Factor	Mechanism of action
HGF and HGF activator^Citation61	Factor secreted by DPC that promotes proliferation of epithelial follicular cells
EGF^Citation60	Promotes growth and migration of follicle ORS cells by activation of Wnt/β-catenin signaling
bFGF^Citation62	Promotes the development of hair follicle
IL-6^Citation93	Involved in WIHN through STAT3 activation
VEGF^Citation72	Promotes perifollicular angiogenesis
TGF-β^Citation63	Stimulates the signaling pathways that regulate hair cycle
IGF-1^Citation69	Promotes proliferation, survival, and migration of hair follicle cells
IGFBP-1 to -6^Citation70	Regulates IGF-1 effects and its interaction with extracellular matrix proteins at the hair follicle level
BMP^Citation23	Maintains DPC phenotype which is crucial for stimulation of hair follicle stem cell
BMPR1a^Citation23	Maintains the proper identity of DPCs that is essential for specific DPC function
M-CSF^Citation71	Involved in wound-induced hair regrowth
M-CSFR^Citation71	Involved in wound-induced hair regrowth
PDGF and PDGFR-β/-α^Citation64	Upregulates the genes involved in hair follicle differentiation. Induction and regulation of anagen phase. PDGF and its receptors are essential for follicular development
Wnt3a^Citation97	Involved in hair follicle development through β-catenin signaling
PGE2^Citation79,Citation80	Stimulates anagen phase in hair follicles
PGF2α and analogs^Citation79,Citation80	Promotes transition from telogen to anagen phase of the hair cycle
BIO^Citation98	GSK-3 inhibitor
PGE2 or inhibition of PGD2 or PGD2 receptor D2/GPR44^Citation77	Promotes follicle regeneration
Iron and l-lysine^Citation95	Under investigation

Abbreviations: bFGF, basic fibroblast growth factor; BIO, (2′Z,3′E)-6-bromoindirubin-3′-oxime; BMP, bone morphogenetic protein; DPCs, dermal papilla cells; EGF, epidermal growth factor; GSK-3, glycogen synthase kinase-3; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor 1; IGFBP-1, insulin-like growth factor-binding protein 1; IL-6, interleukin-6; M-CSF, microphage colony-stimulating factor; M-CSFR, microphage colony-stimulating factor receptor; ORS, outer root sheath; PDGF, platelet-derived growth factor; PDGFR-α, platelet-derived growth factor receptor alpha; PDGFR-β, platelet-derived growth factor receptor beta; PGD2, prostaglandin D2; PGE2, prostaglandin E2; TGF-β1, transforming growth factor β1; VEGF, vascular endothelial growth factor; WIHN, wound-induced hair neogenesis; Wnt3a, wingless-type MMTV integration site family, member 3A.

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