Katherine Kiwimagi
Massachusetts Institute of Technology, USA
Biography
Differentiation of induced pluripotent stem cells (iPSCs) into organoids has been achieved via a plethora of modalities. One of the more common techniques includes developing multi-day culture strategies where morphogenesis and growth factors are added and removed to achieve different differentiation paradigms. This is limited by diffusion and penetration of these small molecules, as well as a uniform application of the signals. Although recent studies involving microfluidics and substrate patterning have achieved a degree of spatial resolution, engineering synthetic genetic programs to be executed within and across cells, promises more and enables spatiotemporal control of cellular differentiation. We have shown that these heterogeneous differentiation programs can yield production of all three germ layers which results in liver like and vascularized organoids. This work hopes to expand on what we have already shown with the development and application of a synthetic cell-cell communication tool box to employ heterogeneous differentiation programs to further organoid development. Synthetic cell-cell communication tools enhance and extend the design of multi-cellular frameworks for tissue construction and differentiation. It is these organotypic like structures, often called organoids that are making their way to the forefront in the development of personalized medicine. One way to program the needed differentiation for organoid maturation is to design multi-cellular circuits. In order to design these circuits capable of coordinated patterns formation one needs tools for cell-cell communication. These cell-cell communication systems are the tools we will need to engineer a better world. This work aims to construct cell-cell communication tools for the construction of programmable spatiotemporal patterns in mammalian cells. This includes the first mammalian synthetic circuit capable of producing its own diffusible signaling molecule that is orthogonal to the endogenous system. Implementation of heterogeneous differentiation programs has allowed for vascularization and development of iPCs derived organoids.