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

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 surrou...

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Autores principales: Park, Junghyun, Jun, Eun Kyoung, Son, Daryeon, Hong, Wonjun, Jang, Jihoon, Yun, Wonjin, Yoon, Byung Sun, Song, Gwonhwa, Kim, In Yong, You, Seungkwon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802618/
https://www.ncbi.nlm.nih.gov/pubmed/31273189
http://dx.doi.org/10.1038/s12276-019-0266-7
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author Park, Junghyun
Jun, Eun Kyoung
Son, Daryeon
Hong, Wonjun
Jang, Jihoon
Yun, Wonjin
Yoon, Byung Sun
Song, Gwonhwa
Kim, In Yong
You, Seungkwon
author_facet Park, Junghyun
Jun, Eun Kyoung
Son, Daryeon
Hong, Wonjun
Jang, Jihoon
Yun, Wonjin
Yoon, Byung Sun
Song, Gwonhwa
Kim, In Yong
You, Seungkwon
author_sort Park, Junghyun
collection PubMed
description 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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spelling pubmed-68026182019-10-25 Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration Park, Junghyun Jun, Eun Kyoung Son, Daryeon Hong, Wonjun Jang, Jihoon Yun, Wonjin Yoon, Byung Sun Song, Gwonhwa Kim, In Yong You, Seungkwon Exp Mol Med Article 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. Nature Publishing Group UK 2019-07-04 /pmc/articles/PMC6802618/ /pubmed/31273189 http://dx.doi.org/10.1038/s12276-019-0266-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Park, Junghyun
Jun, Eun Kyoung
Son, Daryeon
Hong, Wonjun
Jang, Jihoon
Yun, Wonjin
Yoon, Byung Sun
Song, Gwonhwa
Kim, In Yong
You, Seungkwon
Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title_full Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title_fullStr Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title_full_unstemmed Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title_short Overexpression of Nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
title_sort overexpression of nanog in amniotic fluid–derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802618/
https://www.ncbi.nlm.nih.gov/pubmed/31273189
http://dx.doi.org/10.1038/s12276-019-0266-7
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