RESEARCH HIGHLIGHTS CELL BIOLOGY Reproducibly generating organ buds in vitro Coculture of three cell types on hydrogel ers used Matrigel, a mix of extracellular work calls into question what he refers to as with the appropriate stiffness enables the matrix proteins secreted by mouse sarcoma the classical paradigm—that cell aggregates generation of functional organ buds. cells, as the substrate that triggered self- form if the strength of cell-cell adhesion For patients with end-stage organ failure, a organization, but “little is known about its exceeds that of cell-substrate adhesion. The transplant is the only treatment option and is critical components,” says Takebe. “I noticed researchers saw good cell-aggregate forma- often delayed owing to a shortage of donors. that some environmental factors affect liver tion if they cultured the cells on hydrogels The in vitro culture of patient-s pecific organs bud self-organization. I wanted to precisely with moderate stiffness. Yoshikawa con- has long been seen as a solution, as techni- define the physical mechanisms for multi- cludes that “the regulation of cell-substrate cally challenging as it is desirable. Takanori cellular assembly as well as their cellular or interaction using gels can potentially become Takebe of Yokohama City University and molecular mechanisms,” he says. a basic strategy to generate functional organ Hiroshi Yoshikawa of Saitama University, In their new work, the researchers studied bu d s .” The researchers generated vascular- both in Japan, wanted to take in vitro organ the crucial components of the culture system ized organ buds for multiple organs. bud culture beyond proof of principle and by labeling the three cell types with different How long before this culture system yields show that it is a robust method. fluorescent markers and tracking their self- human organs? Takebe says it is possible but Takebe and colleagues had demonstrated assembly into organ buds with time-lapse challenging. “We need a more comprehen- a few years ago that cocultured induced imaging. They saw that MSCs contributed sive understanding of natural human organ- pluripotent stem cell-derived hepatic endo- the contraction force that drives self-organi- ogenesis to move forward,” he says. derm cells, mesenchymal stem cells (MSCs) zation and that substrate stiffness influenced Nicole Rusk and endothelial progenitor cells will self- condensation. RESEARCH PAPERS assemble to form liver organ buds that grow “Fine-tuned cell-substrate mechanical Takebe, T. et al. Vascularized and complex organ buds into a vascularized, functional liver after interaction is one of the keys to generate from diverse tissues via mesenchymal cell–driven ransplantation into a mouse. The research- organ buds,” says Yoshikawa. For him, this condensation. Cell Stem Cell 16, 556–565 (2015). t Nature America, Inc. All rights reserved. America, Inc. Nature 5 © 201 npg 600 | VOL.12 NO.7 | JULY 2015 | NATURE METHODS.