EPFL Doctorate Award - 2022 - Mikhail Nikolaev
Engineering next generation organoids through guided stem cell self-organisation
EPFL thesis n°7568
Thesis director: Prof. M. Lutolf
For his outstanding contributions to the field of stem cell technology. In particular, for the invention of pioneering bioengineering tools to generate advanced stem cell-based organoid models.
One of the long-standing goals in the field of tissue engineering is the fabrication of de novo tissues to provide better organ models for basic research, drug discovery, and to alleviate a shortage of donor organs in the future. In this thesis, three innovative bioengineering technologies were developed that offer the possibility of steering in vitro stem cells culture into more controllable and physiologically relevant miniature organoids and tissues. The aim of the first project was to study how predefined geometric constraints, as they exist in vivo, affect tissue development. This approach allowed the generation of large arrays of the identical organoids, having pre-defined shape and size to study cellular mechanisms involved in the cell type pattering (Science, 2022). The second project was focused on replicating aspects of organ physiology by developing a novel three-dimensional organ-on-chip approach. Using stem cells derived from patient biopsies, this technology enables production of miniature versions of patient’s organs that can be used in personalized diagnostics and medical treatment assays (Nature, 2020). Bioprinting has long been considered as one of the most promising technologies for fabricating organs in vitro. The third project was aimed to develop a new bioprinting strategy that preserves stem cell self-organization potential and extends organoids growth to the macroscopic scale(Nature Materials, 2020). These technologies will become efficient research tools facilitating the translation of organoid technology towards pharmaceutical and clinical applications.