title: Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation.
abstract: Transplantation of in-vitro-generated organ buds is a promising approach toward regenerating functional and vascularized organs. Though it has been recently shown in the context of liver models, demonstrating the applicability of this approach to other systems by delineating the molecular mechanisms guiding organ bud formation is critical. Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine.
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; PRESTO, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan. Electronic address: ttakebe@yokohama-cu.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Takebe
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Enomura
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yoshizawa
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Department of Chemistry, Faculty of Science, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Chemistry, Faculty of Science, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Toyohara
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Osafune
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Chemistry, Faculty of Science, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan. Electronic address: hiroshi@mail.saitama-u.ac.jp.
authors.forename: Hiroshi Y
authors.initials: HY
authors.lastname: Yoshikawa
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018919:Neovascularization, Physiologic; D009924:Organ Culture Techniques; D009928:Organ Specificity; D038081:Organogenesis; D010179:Pancreas / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology*; D044968:Regenerative Medicine; D013234:Stem Cells / Q000502:physiology*; D014180:Transplantation