Abstract
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.
Highlights
Alopecia, the general medical term for hair loss or baldness, is a distressing condition caused by complex factors, including genetic, hormonal, iatrogenic, and traumatic events
We suggest that Nanog is the key transcriptional regulator responsible for the enhanced proliferation of amniotic fluid (AF)-mesenchymal stem cells (MSCs)
Since pluripotency genes are known to regulate the stemness of MSCs and embryonic stem cells (ESCs) by maintaining self-renewal and inhibiting differentiation[20,21], we investigated the endogenous expression of Oct[4] and Sox[2] in AF-N-MSCs to determine whether the enrichment of Nanog protein has a profound effect on the expression of other pluripotency factors
Summary
The general medical term for hair loss or baldness, is a distressing condition caused by complex factors, including genetic, hormonal, iatrogenic, and traumatic events. Hair transplantation is the second-best option for alopecia patients who do not have success with medical therapies; previous studies reported conflicting results due to differences in techniques, skill levels of the surgeons who Official journal of the Korean Society for Biochemistry and Molecular Biology. Park et al Experimental & Molecular Medicine (2019) 51:72 performed the transplant, and characteristics of the patients. Such operations cannot be performed more than three times on the same patient[3]. Increased attention has been paid to developing satisfactory first-line treatments
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