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Int J Mol Sci. 2018 Feb 28;19(3). pii: E691. doi: 10.3390/ijms19030691.

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

Author information

1
College of Pharmacy, Yonsei University, Incheon 21983, Korea. nh147837@gmail.com.
2
STEMORE Co., Ltd., Incheon 21983, Korea. nh147837@gmail.com.
3
College of Pharmacy, Wonkwang University, Iksan 54538, Jeonbuk, Korea. shins@wku.ac.kr.
4
Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 21983, Korea. sunuksong@inha.ac.kr.
5
College of Pharmacy, Yonsei University, Incheon 21983, Korea. brian99@empal.com.
6
STEMORE Co., Ltd., Incheon 21983, Korea. brian99@empal.com.

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.

KEYWORDS:

CXCL1; PD-ECGF; PDGF-C; adipose-derived stem cells; hair growth; minoxidil

PMID:
29495622
PMCID:
PMC5877552
DOI:
10.3390/ijms19030691
[Indexed for MEDLINE]
Free PMC Article

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