Abstract:In vitro models of human hair follicle-like tissue could be fundamental tools to better understand hair follicle morphogenesis and hair drug screening. During prenatal development and postnatal cyclic hair regeneration, hair follicle morphogenesis is triggered by reciprocal interactions and the organization of the epithelial and mesenchymal cell populations. Given this mechanism, we developed an approach to induce hair peg-like sprouting in organoid cultures composed of epithelial and mesenchymal cells. Human … Show more
“…This indicates that the growth mechanism of the IVHF is similar to that of HFs in the body. Finally, after reaching the plateau, hair growth of up to 1.5 mm in length was observed, which is a level that previous studies [58] have not achieved. Overall, these results demonstrate that the SCOC we established has trichogenic potential similar to that of existing hair epithelial cell cultivation conditions.…”
In vitro hair follicle models are currently limited to ex vivo hair follicle organ cultures (HFOC) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a human in vitro hair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolated in vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seen in vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (dermal papilla). Furthermore, the new hair model was able to elongate similarly to ex vivo HFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to s hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to those in vivo were observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.
“…This indicates that the growth mechanism of the IVHF is similar to that of HFs in the body. Finally, after reaching the plateau, hair growth of up to 1.5 mm in length was observed, which is a level that previous studies [58] have not achieved. Overall, these results demonstrate that the SCOC we established has trichogenic potential similar to that of existing hair epithelial cell cultivation conditions.…”
In vitro hair follicle models are currently limited to ex vivo hair follicle organ cultures (HFOC) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a human in vitro hair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolated in vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seen in vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (dermal papilla). Furthermore, the new hair model was able to elongate similarly to ex vivo HFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to s hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to those in vivo were observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.
“…We successfully developed a hair follicle organoid (hair follicloid) that could regenerate hair shafts in vitro with cells of mouse origin 13 , 14 . The application of this approach to cells of human origin showed that immature hair shaft-like structures elongated in response to minoxidil, a typical hair growth-promoting agent 15 . In our previous study, we examined potential hair growth-promoting drug candidates using human hair follicloids and identified the effects of oxytocin on hair growth 6 .…”
Considerable global demand exists for the development of novel drugs for the treatment of alopecia. A recent report demonstrated that oxytocin promotes hair growth activity in human dermal papilla (DP) cells; however, its application in drugs or cosmetic products is challenging because rapid degradation and relatively large molecular weight prevent long-term topical administration on the scalp. Here, we examined cinnamic acid, a small molecule activator for oxytocin receptor (OXTR) expression. Treatment with cinnamic acid led to upregulation of OXTR and trichogenic gene expression in human DP cells. Furthermore, inhibition of OXTR with an antagonist, L-371,257, suppressed hair growth-related gene expression in DP cells. These findings suggest that cinnamic acid enhances the hair growth ability of DP cells via oxytocin signaling. Additionally, we tested the hair growth-promoting effects of cinnamic acid using hair follicle organoids in vitro and observed that cinnamic acid significantly promoted the growth of hair peg-like sprouting. These promising results may be useful for developing hair growth-promoting products targeting oxytocin.
“…Minoxidil, a commercially available hair growth reagent, improves DP cell function to increase the production of growth factors such as VEGF and FGF7 34 , 35 . Since OXT has a similar effect, we hypothesized that OXT might be a candidate for a hair growth reagent and investigated the hair growth ability of OXT using our in vitro hair follicle organoid models 36 . Figure 5 Gene chip analysis and enriched signaling pathway inhibition.…”
Oxytocin (OXT) is a neuropeptide hormone termed “love hormone” produced and released during childbirth and lactation. It is also produced in response to skin stimulation (e.g., during hugging and massaging) and music therapy. The effects of OXT on various organs have been revealed in recent years; however, the relationship between hair follicles and OXT remains unclear. In this study, we examined the effects of OXT on dermal papilla (DP) cells that control hair growth by secreting growth/regression signals. Gene expression analysis revealed that DP signature markers were significantly upregulated in DP cells treated with OXT. In addition, we tested the hair growth-promoting effects of OXT using in vitro hair follicle organoids. OXT promoted the growth of hair peg-like sprouting by upregulating the expression of growth-promoting factors, including genes encoding vascular endothelial growth factor A (VEGFA). This study highlights the positive effects of OXT in hair follicles and may assist in the development of new treatments for alopecia.
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