研究者詳細 - 福田　淳二

The transplantation of pre-vascularized bone grafts is a promising strategy to improve the efficacy of engraftment and bone regeneration. We propose a hydrogel microbead-based approach for preparing vascularized and high-density tissue grafts. Mesenchymal stem cell-encapsulated collagen microgels (2 & mu;L), termed bone beads, were prepared through spontaneous constriction, which improved the density of the mesenchymal stem cells and collagen molecules by more than 15-fold from the initial day of culture. Constriction was attributed to cell-attractive forces and involved better osteogenic differentiation of mesenchymal stem cells than that of spheroids. This approach was scalable, and & SIM;20 0 0 bone beads were prepared semi-automatically using a liquid dispenser and spinner flask. The mechanical stimuli in the spinner flask further improved the osteogenic differentiation of the mesenchymal stem cells in the bone beads compared with that in static culture. Vascular endothelial cells readily attach to and cover the surface of bone beads. The in vitro assembly of the endothelial cell-enveloped bone beads resulted in microchannel formation in the interspaces between the bone beads. Significant effects of endothelialization on in vivo bone regeneration were shown in rats with cranial bone defects. The use of endothelialized bone beads may be a scalable and robust approach for treating large bone defects. A unique aspect of this study is that the hMSC-encapsulated collagen microgels were prepared through spontaneous constriction, leading to the enrichment of collagen and cell density. This constriction resulted in favorable microenvironments for the osteogenic differentiation of hMSCs, which is superior to conventional spheroid culture. The microgel beads were then enveloped with vascular endothelial cells and assembled to fabricate a tissue graft with vasculature in the interspaces among the beads. The significant effects of endothelialization on in vivo bone regeneration were clearly demonstrated in rats with cranial bone defects. We believe that microgel beads covered with vascular endothelial cells provide a promising approach for engineering better tissue grafts for bone-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 licens ( http://creativecommons.org/licenses/by/4.0/ )

In vitro hair follicle growth model for drug testing

Tatsuto Kageyama, Hikaru Miyata, Jieun Seo, Ayaka Nanmo & Junji Fukuda

Scientific Reports 13 2023年3月 [査読有り]

DOI

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）共著

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 … 全著者表示

ACS Biomaterials Science & Engineering 9 ( 3 ) 1510 - 1519 2023年3月 [査読有り]

DOI Web of Science PubMed

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）共著

Hypoxia inducible factor-1α promotes trichogenic gene expression in human dermal papilla cells

Jieun Seo, Lei Yan, Tatsuto Kageyama, Ayaka Nanmo, Yang-Sook Chun & Junji Fukuda

Scientific Reports 13 2023年1月 [査読有り]

DOI

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）共著

Impacts of manipulating cell sorting on in vitro hair follicle regeneration

Kageyama Tatsuto, Anakama Riki, Togashi Hideru, Fukuda Junji

Journal of Bioscience and Bioengineering 134 ( 6 ) 534 - 540 2022年12月 [査読有り]

DOI Web of Science PubMed

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）共著

Optimized Microwell Array Device for Preparation of Hair Follicle Germ-like Aggregates

Kohei Suzuki, Yoshiomi Hiroi, Tatsuto Kageyama, Junji Fukuda

Alternatives to Animal Testing and Experimentation 27 ( 1 ) 14 - 23 2022年10月 [査読有り]

DOI CiNii Research

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：日本動物実験代替法学会単著

Hair follicle morphogenesis is triggered by reciprocal interactions between epithelial and mesenchymal layers in the hair follicle germ. Techniques to create follicle germ-like structures in vitro may be useful for understanding hair follicle morphogenesis and for creating transplantable tissue for hair regenerative medicine. Microwell arrays with oxygen-permeable materials have been proposed as a promising tool for in vitro fabrication of hair follicle germ. In this study, we investigated the effects of microwell morphology and culture process on the formation and function of hair follicle germ. Microwell geometries (flat, round-bottom, pen, and cone) significantly affected the formation of hair follicle germ and the expression of hair growth-related genes. Specifically, pen-type microwells enhanced the rate of follicle germ formation by promoting cell assembly. Even in typical round-bottom wells, centrifugal filling of cells into the microwells enhanced cell assembly and follicular germ formation rates. The higher the efficiency of two cell types to form two separate follicular germ, the higher the expression of hair growth-associated gene, versican. The highest expression of versican was observed when cells were centrifugally packed in round-bottom wells. Aside from hair follicle formation, these microwell array with various shapes may be useful for producing various other organoids and tissues.

Effects of Exosomes Derived from Dermal Papilla Cells on Hair Follicle Stem Cells and Hair Follicle Organoids

Yinghui Zhou, Monami Yamane, Kohei Suzuki, Ayaka Nanmo, Shan Tu, Tatsuto Kageyama, Junji Fukuda

Alternatives to Animal Testing and Experimentation 27 ( 1 ) 1 - 13 2022年10月 [査読有り]

DOI CiNii Research

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：日本動物実験代替法学会単著

Hair follicle development and cycle are regulated by the reciprocal interactions between epithelial and mesenchymal cells. Mechanisms responsible for the regulation have mainly been studied using experimental animals such as rodent fetuses. The purpose of this study is to understand such communications by using in vitro cell culture models of human hair follicle-derived cells. Human dermal papilla cells (DPCs) were cultured using 2-dimensional (2D), spheroid (3D), and spheroid microwell array cultures in an oxygen-permeable substrate (3D-oxy). Exosomes secreted in the culture media were collected and purified. All three types of exosomes moderately promoted proliferation of human hair follicle stem cells (HFSCs). Exosomes from the 3D-oxy culture most efficiently upregulated the expression of CD200, CD34, and K15 in HFSCs compared to those from the other two culture methods. To investigate the effects of exosomes on in vitro hair follicle formation, mouse embryonic epithelial and mesenchymal cells were used to prepare hair follicle organoids. The expression analysis of trichogenic and HFSC marker genes revealed that exosomes from the 3D-oxy culture were the most effective in maintaining stem cells and stimulating hair follicle sprouting in vitro. Exosomes from human DPCs may have substantial potential for treating patients with hair loss.

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction

Kageyama Tatsuto, Shimizu Akihiro, Anakama Riki, Nakajima Rikuma, Suzuki Kohei, Okubo Yusuke, Fukud … 全著者表示

Science Advances 8 ( 42 ) 2022年10月 [査読有り]

DOI Web of Science PubMed

記述言語：英語掲載種別：研究論文（学術雑誌）共著

Bone beads enveloped with vascular endothelial cells for bone regenerative medicine

Tatsuto Kageyama, Hikaru Akieda, Yukie Sonoyama, Ken Sato, Hiroshi Yoshikawa, Hitoshi Isono, Makoto … 全著者表示

Acta Biomaterialia 2022年8月 [査読有り]

DOI

記述言語：英語掲載種別：研究論文（学術雑誌）単著

Co-Culture of THP-1 Cells and Normal Human Epidermal Keratinocytes (NHEK) for Modified Human Cell Line Activation Test (h-CLAT)

Sawada Yuka, Tsukumo Hanae, Fukuda Junji, Iijima Kazutoshi, Itagaki Hiroshi

Applied Sciences 12 ( 12 ) 2022年6月 [査読有り]

<福田 淳二>

論文 - 福田 淳二

<福田　淳二>

論文 - 福田　淳二