Periodic Reporting for period 2 - MicroAdiPSChip (Micro-Fat Tissue on Chip)
Reporting period: 2019-12-01 to 2021-05-31
To investigate tissue architectural influences on fat cell development, we proposed to generate an assembling method for complex micro-fat tissue on a chip. Here, our working hypothesis was that paracrine communication between stem cells and cells of the perivascular microenvironment define the developmental fat cell trajectory. Therefore, we induced the development of adipocytes, endothelial and pericytes from the same human pluripotent stem cells. From the latter two cell types, we were able to generate functional vessels in vitro. In addition, single cell transcriptomic analysis of the vessel formation process in a chip-compatible hydrogel revealed the major cell-cell interaction proteins required for establishing these vessels. In combination with our new open microfluidic chip platform, we will exploit the molecular knowledge of vessel formation to generate vascularized stem cell-derived white adipose tissue on a chip. Through changes in the cell type composition and spatial organization of the vascularized adipose tissue, we will investigate if we can induce “browning” of the tissue solely by modifications of the its architecture.
1) The generation of two new microfluidic chip platforms for long-term culturing and processing 3D of human stem cell cultures
2) A new additive manufacturing technology for microfluidic chip production
3) A differentiation platform to derive white adipocytes from human induced pluripotent stem cell in high yield
4) The engineering of vascularized human adipose tissue on chip
5) A single cell study of in vitro blood vessel formation from stem cell-derived endothelial cells within chip compatible hydrogel
With these advances, we set the foundation to provide much needed insights into adipocyte cell type development and therewith create the basis for new strategies for obesity therapies as proposed.