Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation

Takanori Takebe, Masahiro Enomura, Emi Yoshizawa, Masaki Kimura, Hiroyuki Koike, Yasuharu Ueno, Takahisa Matsuzaki, Takashi Yamazaki, Takafumi Toyohara, Kenji Osafune, Hiromitsu Nakauchi, Hiroshi Y. Yoshikawa, Hideki Taniguchi

Research output: Contribution to journalArticlepeer-review

220 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)556-565
Number of pages10
JournalCell Stem Cell
Volume16
Issue number5
DOIs
Publication statusPublished - 2015 May 7
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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