The microfluidic research group led by Prof. QIN Jianhua from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences developed a novel human islet organoid-on-a-chip to generate islet organoids from human induced pluripotent stem cells (hiPSCs). The results were published in Lab on a chip (DOI: 10.1039/C8LC01298A) as a cover article.
hPSCs-derived organoids have represented a new class of in vitro organ models for development biology studies, disease modeling and regenerative medicine. Study in stem cell organoids has facilitated high-fidelity modeling of the original tissue or organ via self-renewal and self-organization. These organoids can recapitulate the organ specific functions, cellular architecture and morphologies.
Diabetes mellitus caused by damaged pancreatic islets leads to an increase in morbidity and mortality. Rebuilding biomimetic human islet organoids in vitro provides promising platform for diabetes studies, cell replacement treatment and drug screening, which remains challenging.
In this work, the scientists presented a new strategy to engineer human islet organoids by combining developmental biology and bioengineering principles.
The engineered organ-on-a-chip system contained a multi-layer microfluidic device that allowed for controllable aggregation of embryoid bodies (EBs), in situ pancreatic differentiation and generation of islet organoids under perfused 3D culture in a single device. The generated islet organoids contained heterogeneous islet-specific α and β-like cells that exhibited favorable growth and cell viability. They also exhibited more sensitive glucose-stimulated insulin secretion (GSIS) and higher Ca2+ flux, indicating the role of biomimetic mechanical flow in promoting endocrine cell differentiation and maturation of islet organoids.
This human islet organoid-on-a-chip provided a proof of concept for synergistic engineering of organoids by combining bioengineering technology and stem cell development biology. This platform could be further integrated with additional microfluidic elements, advanced materials and biosensors to facilitate organoids maturation in a biomimetic microenvironment and functional monitoring, providing a promising platform for organoid engineering, drug testing and regenerative medicine.
This research was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences. This paper was dedicated to the 70th anniversary of Dalian Institute of Chemical Physics, CAS. (Text by TAO Tingting)