TY - JOUR
T1 - Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation
AU - Takebe, Takanori
AU - Enomura, Masahiro
AU - Yoshizawa, Emi
AU - Kimura, Masaki
AU - Koike, Hiroyuki
AU - Ueno, Yasuharu
AU - Matsuzaki, Takahisa
AU - Yamazaki, Takashi
AU - Toyohara, Takafumi
AU - Osafune, Kenji
AU - Nakauchi, Hiromitsu
AU - Yoshikawa, Hiroshi Y.
AU - Taniguchi, Hideki
PY - 2015/5/7
Y1 - 2015/5/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929166388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929166388&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2015.03.004
DO - 10.1016/j.stem.2015.03.004
M3 - Article
C2 - 25891906
AN - SCOPUS:84929166388
VL - 16
SP - 556
EP - 565
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 5
ER -