Type 2 diabetes (T2DM) is a systematic multi-organ metabolic disorder characterized by dynamic interactions between different organs.
The islets-liver axis are closely associated with normal glucose regulation and homeostasis. Dysfunction of the interactions between these organs can lead to the progression of type 2 diabetes.
Recently, a group led by Professor Qin Jianhua of the Dalian Institute of Chemical Physics (DICP) at the Chinese Academy of Sciences (CAS) has developed a human-guided multiorganoid system. Pluripotent stem cells (HiPSCs) Simulates the human liver-islet axis in normal and type 2 diabetes.
This study was published in Advanced science December 23, 2021.
“Organoids derived from stem cells, a new class of 3D tissue, have important structural and functional features of their in vivo counterparts,” said Professor Qin.
This newly developed multi-organoid system simulates the human liver-islet axis in physiological and pathological conditions, enabling 3D co-culture of hiPSC-derived liver and islet organoids for up to 30 days.
Researchers have found that the produced liver and pancreatic islet organoids exhibit favorable growth and improved tissue-specific function in this perfused microfluidic 3D culture system.
“Sensitive glucose stimulation Insulin secretion It is from islet organoids and has increased glucose utilization of liver organoids. ” This reflects the coordinated interaction between the two organs in this perfusion co-culture system.
Transcriptional analysis revealed that activated signaling pathways are associated with glucose / CYP450 metabolism and glycolysis / gluconeogenesis in liver and islet organoids.
In addition, this microfluidic islet liver Organoid System exhibition Mitochondrial dysfunction Decreased glucose transporter capacity in hyperglycemic conditions. This may be due to alleviation by treatment with anti-diabetes drugs.
“This new system is Feedback loop Within the liver-islet axis, there is also a relevant response to high glucose and anti-diabetes drugs, which cannot be easily achieved with traditional cell culture and animal models, “said Professor Hata. Overview of complex T2DM etiology and drug development. ”
Tingting Tao et al, a microengineering multiorganoid system from hiPSC for reproducing the human hepatopancreatic islet axis in normal and type 2 diabetes, Advanced science (2021). DOI: 10.1002 / advs.202103495
Chinese Academy of Sciences
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