Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

Abstract

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

HB-EGF Improves the Hair Regenerative Potential of Adipose-Derived Stem Cells via ROS Generation and Hck Phosphorylation

“…THPO may be an important place for megakaryocytopoiesis in blood vessels [24]. Interestingly, vasodilators such as minoxidil and udenfil stimulated ASC motility, thereby inducing hair growth [25,26]. The relationship between the THPO level, vasodilation, and hair growth should be further studied.…”

Harnessing the Power of Regenerative Therapy for Vitiligo and Alopecia Areata

“…Initially developed for the treatment of male-and femalepattern baldness, minoxidil is now widely used off-label for the treatment of many types of hair loss including AA. It exerts its effects by inducing growth factors from DP cells (vascular endothelial growth factor, hepatocyte growth factor, and IGF-1); activating the DP b-catenin pathway; increasing blood flow by dilating HF arteries, resulting in induction and prolongation of anagen (Otomo, 2002); and stimulating the telogen-to-anagen induction (Choi et al, 2018) (Figure 1c and d). Several placebo-controlled studies have shown minoxidil to stimulate hair growth in patients with AA when applied daily (El Taieb et al, 2016;Price, 1987), although cosmetically acceptable results were not often obtained with minoxidil as a monotherapy.…”

Transdermal delivery of Minoxidil using HA-PLGA nanoparticles for the treatment in alopecia

“…Minoxidil (MXD) is the most widely used drug in alopecia treatment, especially male-pattern hair loss [1][2][3][4][5][6][7]. It is known to have a vasodilatory effect and expedite secretion of growth factors for hair regeneration.…”

“…Due to the characteristics of alopecia, it works effectively when applied to the topical skin area through transdermal delivery of MXD. However, typical MXD delivery has the disadvantages of low efficiency of transdermal delivery and various side effects, such as tolerance, inflammation and low blood pressure [6]. Therefore, many studies have been investigated to improve the transdermal delivery efficiency of MXD applied to the skin and the therapeutic efficacy in alopecia, through the transdermal routes such as hair follicles, sweat glands or microneedle arrays [2,4,[7][8][9][10].…”