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KMID : 0620920190510070072
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Experimental & Molecular Medicine
2019 Volume.51 No. 7 p.72 ~ p.72
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Overexpression of Nanog in amniotic fluid?derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
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Park Jung-Hyun
Jun Eun-Kyoung
Son Da-Ryeon
Hong Won-Jun
Jang Ji-Hoon
Yun Won-Jin
Yoon Byung-Sun
Song Gwon-Hwa
Kim In-Yong
You Seung-Kwon
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Abstract
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Alopecia, one of the most common chronic diseases, can seriously affect a patient’s psychosocial life. Dermal papilla (DP) cells serve as essential signaling centers in the regulation of hair growth and regeneration and are associated with crosstalk between autocrine/paracrine factors and the surrounding environment. We previously demonstrated that amniotic fluid?derived mesenchymal stem cell?conditioned medium (AF-MSC-CM) accelerates hair regeneration and growth. The present study describes the effects of overexpression of a reprogramming factor, Nanog, on MSC properties, the paracrine effects on DP cells, and in vivo hair regrowth. First, we examined the in vitro proliferation and lifespan of AF-MSCs overexpressing reprogramming factors, including Oct4, Nanog, and Lin28, alone or in combination. Among these factors, Nanog was identified as a key factor in maintaining the self-renewal capability of AF-MSCs by delaying cellular senescence, increasing the endogenous expression of Oct4 and Sox2, and preserving stemness. Next, we evaluated the paracrine effects of AF-MSCs overexpressing Nanog (AF-N-MSCs) by monitoring secretory molecules related to hair regeneration and growth (IGF, PDGF, bFGF, and Wnt7a) and proliferation of DP cells. In vivo studies revealed that CM derived from AF-N-MSCs (AF-N-CM) accelerated the telogen-to-anagen transition in hair follicles (HFs) and increased HF density. The expression of DP and HF stem cell markers and genes related to hair induction were higher in AF-N-CM than in CM from AF-MSCs (AF-CM). This study suggests that the secretome from autologous MSCs overexpressing Nanog could be an excellent candidate as a powerful anagen inducer and hair growth stimulator for the treatment of alopecia.
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KEYWORD
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Mesenchymal stem cells, Regeneration, Self-renewal
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