The clonal evolution model and the cancer stem cell model are two independent models of cancers, yet recent data shows intersections between the two models. This article explores the impacts of the CSC model on the CE model. I show that CSC restriction, which depends on CSC frequency in cancer cell populations and on the probability of dedifferentiation of cancer non-stem cells into CSCs, can favor or impede some patterns of evolution and some processes of evolution. Taking CSC restriction into (...) account for the CE model thus has implications for the way in which we understand the patterns and processes of evolution, and can also provide new leads for therapeutic interventions. (shrink)

Organoids and organs-on-a-chip are currently the two major families of 3D advanced organotypic in vitro culture systems, aimed at reconstituting miniaturized models of physiological and pathological states of human organs. Both share the tenets of the so-called “three-dimensional thinking”, a Systems Physiology approach focused on recapitulating the dynamic interactions between cells and their microenvironment. We first review the arguments underlying the “paradigm shift” toward three-dimensional thinking in the in vitro culture community. Then, through a historically informed account of the technical (...) affordances and the epistemic commitments of these two approaches, we highlight how they embody two distinct experimental cultures. We finally argue that the current systematic effort for their integration requires not only innovative “synergistic” engineering solutions, but also conceptual integration between different perspectives on biological causality. (shrink)