Stem Cell-Derived Insulin-Producing Cells in 3D Engineered Tissue in a Perfusion Flow Bioreactor

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Diabetes Research

Background:

• Pluripotent stem cell-derived insulin-producing cells (IPCs) offer a potential alternative to donor pancreases for type 1 diabetes treatment.
• Maintaining long-term viability and functional stability of *in vitro* cultured IPCs remains a significant challenge.

Purpose of the Study:

• To establish a 3D microenvironment using tissue engineering and a perfusion bioreactor for long-term *in vitro* culture of mouse embryonic stem cell-derived IPCs.
• To evaluate the impact of perfusion flow on the survival, function, and maturation of stem cell-derived IPCs.

Main Methods:

• Development of a 3D engineered tissue system incorporating IPCs derived from mouse embryonic stem cells.
• Comparison of IPC culture under static 3D conditions versus 3D culture with continuous low perfusion flow (0.02 mL/min).
• Assessment of IPC viability, glucose responsiveness, and gene expression (Ins1) over time.

Main Results:

• Static 3D culture led to a gradual decrease in IPC viability over time.
• Continuous low perfusion flow significantly enhanced IPC survival and demonstrated improved function.
• IPCs cultured under perfusion flow exhibited enhanced glucose responsiveness and increased Ins1 expression compared to static cultures.

Conclusions:

• A 3D engineered tissue environment combined with perfusion flow is feasible and beneficial for long-term *in vitro* culture of stem cell-derived IPCs.
• This system provides a valuable platform for investigating biophysical cues that promote IPC function and maturation.
• The findings advance pancreatic tissue engineering and hold potential for future diabetes therapeutics.