During the MicroAdiPSChip funding period, we achieved several research milestones.
Engineering Achievements: We developed microfluidic chip technologies for 3D adipocyte tissue models, methods to assemble adipose tissues with different architectures, and optically controlled hydrogels for tissue printing. We also advanced techniques for single-cell transcriptome analysis with spatial data. By enhancing microfluidic large-scale integration (mLSI) for 3D cell cultures, we created platforms supporting numerous cell culture chambers, successfully culturing hiPSCs in 3D. This optimized differentiation protocols, reducing off-target effects and material use. Additionally, we integrated automated imaging workflows for high-throughput analysis of 3D cultures, improving immunofluorescence histology and label-free imaging throughput.
Biological Achievements: Using mLSI technology, we differentiated human adipocytes from patient-derived stromal vascular fractions in 3D cultures, simulating periodic food intake andrevealing a shift from white to beige adipocytes. To overcome challenges with differentiating hiPSCs into mature adipocytes, we developed vascularized adipocyte organoids. Additionally, we applied our advancements in cell culture technology to generate pancreatic ductal organoids, further advancing pancreatic cancer models. Our new Organ-on-Chip (OoC) platform enabled the integration of advanced technologies, such as single-cell RNA sequencing. The Vessel-on-Chip model demonstrated endothelial cell maturation and arterial toning, supporting research in vascular biology.
Finally, we developed xDBiT, a cost-effective spatial transcriptomics method that improves gene counts and resolution. This technology has been applied to studies on aging and liver function under a high-fat diet, providing new insights into liver zonation.
In summary, our work highlights the significant impact of advanced microfluidic and organoid technologies on addressing complex biological challenges, especially in the creation of clinically relevant tissue models.
