Papers - Yan Lei
about 18-
The role of lipids in promoting hair growth through HIF-1 signaling pathway
Seo, J; Matsumoto, K; Nanmo, A; Tu, S; Jeong, D; Chun, YS; Yan, L; Kageyama, T; Fukuda, J
SCIENTIFIC REPORTS 15 ( 1 ) 2025.2 [Reviewed]
Language：English Publishing type：Research paper (scientific journal) Joint Work
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Effects of oxytocin receptor agonists on hair growth promotion
Kageyama, T; Seo, J; Yan, L; Fukuda, J
SCIENTIFIC REPORTS 14 ( 1 ) 2024.10
Language：English Publishing type：Research paper (scientific journal) Joint Work
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Kageyama, T; Seo, J; Yan, L; Fukuda, J
SCIENTIFIC REPORTS 14 ( 1 ) 2024.2 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Portfolio Joint Work
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.
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Effects of oxytocin on the hair growth ability of dermal papilla cells
Kageyama, T; Seo, J; Yan, L; Fukuda, J
SCIENTIFIC REPORTS 13 ( 1 ) 15587 2023.10 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Portfolio Joint Work
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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Gelatin acrylamide with improved UV crosslinking and mechanical properties for 3D biofabrication
Molino Binbin Zhang, O'Connell Cathal, Kageyama Tatsuto, Yan Lei, Wu Yumeng, Kawamura Izuru, Maruo … Show more authors
Molino Binbin Zhang, O'Connell Cathal, Kageyama Tatsuto, Yan Lei, Wu Yumeng, Kawamura Izuru, Maruo Shoji, Fukuda Junji Hide authors
JOURNAL OF BIOSCIENCE AND BIOENGINEERING 136 ( 1 ) 51 - 57 2023.7 [Reviewed]
Language：English Publishing type：Research paper (scientific journal) Joint Work
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Gelatin acrylamide with improved UV crosslinking and mechanical properties for 3D biofabrication
Molino Binbin Zhang, O'Connell Cathal, Kageyama Tatsuto, Yan Lei, Wu Yumeng, Kawamura Izuru, Maruo … Show more authors
Molino Binbin Zhang, O'Connell Cathal, Kageyama Tatsuto, Yan Lei, Wu Yumeng, Kawamura Izuru, Maruo Shoji, Fukuda Junji Hide authors
Journal of Bioscience and Bioengineering 136 ( 1 ) 51 - 57 2023.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Society for Biotechnology, Japan Joint Work
Photocrosslinkable gelatin has attracted increasing interest in the field of biofabrication, with the most studied and widely used photocrosslinkable gelatin being gelatin methacrylate (GelMa). However, the 3D fabrication of GelMa has presented several limitations and challenges, primarily due to its slow crosslinking speed. It is generally known that acryl-based functional groups have faster reaction kinetics than methacryl-base groups. However, gelatin acrylamide (GelAc) has not been widely investigated, largely due to its increased complexity of synthesis relative to GelMA. In this study, we developed a novel synthesis method for GelAc. By varying the reaction ratio of reagents, GelAc with a degree of substitution from 20% to 95% was produced. The UV crosslinking properties of GelAc was studied, demonstrating significantly faster crosslinking kinetics than GelMa, especially at lower concentrations and low photoinitiator concentrations. The swelling ratio and mechanical properties of the crosslinked GelAc hydrogel were also characterized, and biocompatibility experiments conducted via both surface seeding and hydrogel encapsulation of cells, with good cell viability observed. The application of GelAc for 3D biofabrication was demonstrated by 3D printing. GelAc can be a useful material for the fabrication of 3D conduits for tissue engineering applications. & COPY; 2023, The Society for Biotechnology, Japan. All rights reserved.
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Expansion Culture of Hair Follicle Stem Cells through Uniform Aggregation in Microwell Array Devices
Hirano Sugi, Kageyama Tatsuto, Yamanouchi Maki, Yan Lei, Suzuki Kohei, Ebisawa Katsumi, Kasai Keiic … Show more authors
Hirano Sugi, Kageyama Tatsuto, Yamanouchi Maki, Yan Lei, Suzuki Kohei, Ebisawa Katsumi, Kasai Keiichiro, Fukuda Junji Hide authors
ACS BIOMATERIALS SCIENCE & ENGINEERING 9 ( 3 ) 1510 - 1519 2023.3 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：American Chemical Society Joint Work
Hair regeneration using hair follicle stem cells (HFSCs) and dermal papilla cells is a promising approach for the treatment of alopecia. One of the challenges faced in this approach is the quantitative expansion of HFSCs while maintaining their hair induction capacity. In this study, HFSC expansion was achieved through the formation of uniform-diameter cell aggregates that were subsequently encapsulated in Matrigel. We designed a microwell array device, wherein mouse HFSCs were seeded, allowed to form loosely packed aggregates for an hour, and then embedded in Matrigel. Quantitative analysis revealed a 20-fold increase in HFSC number in 2 weeks through this culture device. Gene expression of trichogenic stem cell markers in the device-grown cells showed a significant increase compared with that of typical flat substrate Matrigel suspension culture cells. These microwell array cultured HFSCs mixed with freshly isolated embryonic mesenchymal cells indicated vigorous hair regeneration on the skin of nude mice. Furthermore, we examined the feasibility of this approach for the expansion of human HFSCs from androgenetic alopecia patients and found that the ratio of CD200+ cells was improved significantly in comparison with that of cells cultured in a typical culture dish or in a Matrigel suspension culture on a flat substrate. Therefore, the novel approach proposed in this study may be useful for HFSC expansion in hair regenerative medicine.
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Hypoxia inducible factor-1α promotes trichogenic gene expression in human dermal papilla cells
13 ( 1 ) 1478 2023.1
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Joint Work
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Luciferase assay system to monitor fibroblast growth factor signal disruption in human iPSCs
Seiya Kanno, Kashu Mizota, Yusuke Okubo, Tatsuto Kageyama, Lei Yan, Junji Fukuda
STAR Protocols 3 ( 2 ) 101439 2022.6 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Single Work
We describe a protocol for a live-cell luciferase assay system for continuously monitoring fibroblast growth factor (FGF) signal disruption in human-induced pluripotent stem cells (iPSCs). Signal disrupting effects of chemicals are used as an indicator to evaluate toxicity. The assay is reliably predictive of the effects of limb malformation chemicals (AUC = 0.93). The current approach is limited to FGF signal disruption, and combinations with other types of signaling will be required to detect the effects of different toxicants. For complete details on the use and execution of this protocol, please refer to Kanno et al. (2022a).
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Bioprinting of hair follicle germs for hair regenerative medicine
Ayaka Nanmo, Lei Yan, Tomoki Asaba, Licheng Wan, Tatsuto Kageyama, Junji Fukuda
Acta Biomaterialia 165 50 - 59 2022.6 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Science Ltd. Single Work
Hair regenerative medicine is a promising approach to treat hair loss. The replication of in vivo tissue con-figurations and microenvironments, such as hair follicle germs, has been studied to prepare tissue grafts for hair regenerative medicine. However, such approaches should be scalable, because a single patient with alopecia requires thousands of tissue grafts. In this paper, we propose an approach for the scalable and automated preparation of highly hair-inductive tissue grafts using a bioprinter. Two collagen droplets (2 & mu;L each) containing mesenchymal and epithelial cells were placed adjacent to each other to fabricate hair-follicle-germ-like grafts. During three days of culture, the pairs of microgel beads were spontaneously contracted by cell traction forces, whereas the two cell types remained separated, where the densities of the cells and collagen were enriched more than 10 times. This approach allowed us to fabricate submil-limeter objects printed with millimeter-order accuracy, facilitating scalable and automated tissue graft preparation. Because of mesenchymal-epithelial interactions, hair microgels (HMGs, i.e., collagen-and cell-enriched microgels) efficiently regenerate hair follicles and shafts when transplanted into the back skin of mice. However, the generated hair shafts mostly remain under the skin. Therefore, we printed microgel beads onto surgical suture guides arrayed on a stage. The microgel beads were contracted along with the suture guides in culture prior to transplantation. The guide-inserted HMGs significantly im-proved hair-shaft sprouting through the skin, owing to the control of the orientation of the HMGs trans-planted into the skin. This approach is a promising strategy to advance hair regenerative medicine.Statement of significance This study proposes an approach for the scalable and automated preparation of highly hair-inductive grafts using a bioprinter. Two collagen droplets containing mesenchymal and epithelial cells were placed adjacently. Cell traction forces caused the pairs of microgel beads to spontaneously contract in culture. Because of mesenchymal-epithelial interactions, hair microgels (HMGs) efficiently regenerated hair fol-licles on the back skin of mice. However, the generated hair shafts remained mostly beneath the skin. Therefore, we printed microgel beads onto surgical suture guides arrayed on a stage. The guide-inserted HMGs significantly improved hair-shaft sprouting through the skin owing to the control of the orientation of the HMGs in the skin. This approach represents a promising strategy for advancing hair regenerative medicine.& COPY; 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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ELECTRICAL STIMULATION VIA CONDUCTIVE POLYMER BED FOR HAIR FOLLICLE STEM CELL CULTURE
Yan Lei, Kageyama Tatsuto, Zhang Binbin, Fukuda Junji
TISSUE ENGINEERING PART A 28 S310 - S310 2022.4
Language：Japanese Publishing type：Research paper (scientific journal) Joint Work
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Electrical stimulation to human dermal papilla cells for hair regenerative medicine
Yan Lei, Kageyama Tatsuto, Zhang Binbin, Yamashita Seiya, Molino Paul J., Wallace Gordon G., Fukuda … Show more authors
Yan Lei, Kageyama Tatsuto, Zhang Binbin, Yamashita Seiya, Molino Paul J., Wallace Gordon G., Fukuda Junji Hide authors
JOURNAL OF BIOSCIENCE AND BIOENGINEERING 133 ( 3 ) 281 - 290 2022.3 [Reviewed]
Language：English Publishing type：Research paper (scientific journal) Joint Work
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133 ( 3 ) 291 - 299 2022.3
DOI Web of Science PubMed CiNii Research
Language：Japanese Publishing type：Research paper (scientific journal) Joint Work
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Yan Lei, Kageyama Tatsuto, Zhang Binbin, Yamashita Seiya, Paul J. Molino, Gordon G. Wallace, Fukuda … Show more authors
Yan Lei, Kageyama Tatsuto, Zhang Binbin, Yamashita Seiya, Paul J. Molino, Gordon G. Wallace, Fukuda Junji Hide authors
Journal of Bioscience and Bioengineering 133 ( 3 ) 281 - 290 2022.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Society for Biotechnology, Japan Joint Work
Hair follicle dermal papilla cells (DPCs) are specialized mesenchymal cells that play pivotal roles in hair formation, growth, and cycles, and they are considered as a cell source in hair regenerative medicine. Rodent dermal papilla cells have been shown to induce de novo hair follicle generation in the skin of recipients following transplantation, suggesting that dermal papilla cells can reprogram epidermal microenvironments. However, human DPCs (hDPCs) lose their ability to generate de novo hair follicles under conventional culture methods. We investigated the effects of electrical stimulation (ES) on hDPCs to restore the depressed trichogenic activity. We demonstrated that ES with a polypyrrole (PPy)-modified electrode upregulated trichogenic gene expression in hDPCs in vitro, and the activated cells when transplanted into mice generated double the number of hairs compared to that without the ES. Using specific inhibitors, we revealed that the mechanisms behind the electrical activation are associated with voltage-gated ion channels. Further, ES can be adapted for hDPCs from a patient with androgenic alopecia. Thus, this approach is potentially beneficial in preparing hDPCs for hair regenerative medicine.
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Kanno Seiya, Okubo Yusuke, Kageyama Tatsuto, Yan Lei, Kitajima Satoshi, Fukuda Junji
ISCIENCE 25 ( 2 ) 103770 2022.2
DOI Web of Science PubMed CiNii Research
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cell Press Joint Work
The number of man-made chemicals has increased exponentially recently, and exposure to some of them can induce fetal malformations. Because complex and precisely programmed signaling pathways play important roles in develop-mental processes, their disruption by external chemicals often triggers develop-mental toxicity. However, highly accurate and high-throughput screening assays for potential developmental toxicants are currently lacking. In this study, we pro-pose a reporter assay that utilizes human-induced pluripotent stem cells (iPSCs) to detect changes in fibroblast growth factor signaling, which is essential for limb morphogenesis. The dynamics of this signaling after exposure to a chemical were integrated to estimate the degree of signaling disruption, which afforded a good prediction of the capacity of chemicals listed in the ECVAM International Validation Study that induce limb malformations. This study presents an initial report of a human iPSC-based signaling disruption assay, which could be useful for the screening of potential developmental toxicants.
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Nakajima Rikuma, Tate Yoshiki, Yan Lei, Kageyama Tatsuto, Fukuda Junji
JOURNAL OF BIOSCIENCE AND BIOENGINEERING 131 ( 6 ) 679 - 685 2021.6 [Reviewed]
DOI Web of Science PubMed CiNii Research
Language：English Publishing type：Research paper (scientific journal) Publisher：Society for Biotechnology, Japan Joint Work
Hair regenerative medicine has emerged as a promising treatment strategy for severe hair loss, such as end-stage androgenetic alopecia. Various approaches to engineering three-dimensional tissue grafts have been explored since they drive the ability to regenerate hair follicles when transplanted. In the present study, we demonstrated the assembly of human adipose-derived stem cells (hASCs) into hair follicle germ (HFG)-like aggregates for de novo hair regeneration. We mixed human dermal papilla cells (hDPCs), murine embryonic epithelial cells, and hASCs in suspension, and allowed them to form aggregates. During three days of culture, cells initially formed a single aggregate with a random distribution of the three cell types, but the epithelial and dermal papilla cells subsequently separated from each other and formed a dumbbell-shaped HFG, with hASCs localized on the hDPC aggregate side. The involvement of hASCs significantly increased gene expression associated with hair morphogenesis compared to HFGs without hASCs. The self-organization of the three cell types was observed in our scalable lab-made chip device. HFGs containing hASCs efficiently generated hair shafts upon transplantation to nude mice, while only a few shafts were generated with HFGs without hASCs. This approach may be a promising strategy for fabricating tissue grafts for hair regenerative medicine. (C) 2021, The Society for Biotechnology, Japan. All rights reserved.
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Kageyama Tatsuto, Nanmo Ayaka, Yan Lei, Nittami Tadashi, Fukuda Junji
JOURNAL OF BIOSCIENCE AND BIOENGINEERING 130 ( 6 ) 666 - 671 2020.12
Language：Japanese Publishing type：Research paper (scientific journal) Joint Work
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Preparation of hair beads and hair follicle germs for regenerative medicine
Tatsuto Kageyama, Lei Yan, Akihiro Shimizu, Shoji Maruo, Junji Fukuda
Biomaterials 212 55 - 63 2019.8 [Reviewed]
Language：English Publishing type：Research paper (scientific journal) Single Work