Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in...

Area of Science:

• Vascular Biology
• Gastroenterology
• Biomedical Engineering

Background:

• Small intestine (SI) vasculature development and function are understudied due to a lack of specific markers and limitations of traditional cell culture.
• Existing methods fail to replicate the mechanobiologic stimuli crucial for vessel development.

Purpose of the Study:

• To construct and characterize a 3D in vitro microfluidic model for studying SI vasculature.
• To investigate the angiogenic properties of intestinal subepithelial myofibroblasts (ISEMFs).
• To incorporate perfused vasculature into a gut-on-a-chip (GOC) model for precision medicine.

Main Methods:

• Development of a 3D microfluidic model supporting co-culture of patient-derived ISEMFs and endothelial cells (ECs).
• Assessment of vascular response to oxygen tension, cell density, growth factors, and Erlotinib.
• Co-culture of ISEMFs and ECs with patient-derived human intestinal epithelial cells (HIECs) within a GOC system.

Main Results:

• ISEMFs and ECs formed perfused capillary networks in the microfluidic model.
• The model demonstrated ISEMFs' angiogenic properties, facilitating reproducible vasculature development.
• The study successfully integrated perfused vasculature into a patient-derived GOC model.

Conclusions:

• ISEMFs possess significant angiogenic potential, enabling the development of functional vasculature in vitro.
• The developed microfluidic GOC model provides a platform for studying SI vasculature and personalized medicine.
• This model holds translational relevance for precision medicine research in gastrointestinal diseases.