Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration

• Published in: Experimental & molecular medicine Vol. 51; no. 7; pp. 1 - 15
• Main Authors: Park, Junghyun, Jun, Eun Kyoung, Son, Daryeon, Hong, Wonjun, Jang, Jihoon, Yun, Wonjin, Yoon, Byung Sun, Song, Gwonhwa, Kim, In Yong, You, Seungkwon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.07.2019; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/1; 13/100; 13/109; 13/31; 14/35; 14/63; 38/61; 38/77; 38/79; 631/532/2074; 631/532/2441; 631/532/489; 64/60; 96; Alopecia; Alopecia - pathology; Alopecia - therapy; Amniotic fluid; Amniotic Fluid - metabolism; Animals; Autocrine signalling; Autografts; Biomedical and Life Sciences; Biomedicine; Cell Proliferation; Cell self-renewal; Cells, Cultured; Cellular Senescence; Chronic illnesses; Dermis - metabolism; Female; Fibroblast growth factor 2; Follicles; Gene Expression; Hair - physiology; Hair Follicle - physiology; Hair loss; Humans; Insulin-like growth factors; Life span; Medical Biochemistry; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice, Inbred C57BL; Molecular Medicine; Nanog Homeobox Protein - genetics; Nanog Homeobox Protein - metabolism; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Paracrine signalling; Platelet-derived growth factor; Regeneration; Secretome; Senescence; Skin; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-019-0266-7

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. Alopecia: Stimulating hair growth via stem cell-based therapy A treatment developed using stem cells that express high levels of a hair-growth-stimulating protein could help treat alopecia. Cells at the base of hair follicles secrete signaling molecules that help maintain follicle stem cell populations and stimulate hair growth, but defects in these signaling pathways can trigger alopecia. Potential treatments created using stem cells derived from amniotic fluid are being explored by Gwonhwa Song, In Yong Kim and Seungkwon You at the College of Life Sciences and Biotechnology, Seoul, South Korea. They have demonstrated that a protein called Nanog found in amniotic fluid-derived stem cell populations can help maintain stem cell health and stimulate secretion of hair growth proteins. These findings led them to develop a topical treatment with medicines derived from stem cells overexpressing Nanog, which triggered dermal cell proliferation and hair regrowth in mice.