Engineering pulmonary vasculature in decellularized rat and human lungs

Area of Science:

• Regenerative Medicine
• Bioengineering
• Stem Cell Therapy

Background:

• Lung transplantation relies on donor organs, facing limitations like organ shortage and immune rejection.
• Bioengineered lungs using patient-derived cells could offer a personalized alternative for transplantation.

Purpose of the Study:

• To regenerate functional pulmonary vasculature in decellularized lung scaffolds using induced pluripotent stem cell-derived cells.
• To develop and optimize methods for efficient cell delivery, vascular maturation, and scaffold repopulation.

Main Methods:

• Decellularized rat and human lung scaffolds were repopulated with endothelial and perivascular cells derived from induced pluripotent stem cells (iPSCs).
• Improved cell delivery and a two-phase culture protocol involving co-seeding of endothelial and perivascular cells were employed.
• Regenerated vascular function was assessed through in vitro measurements and in vivo orthotopic transplantation in rats.

Main Results:

• Achieved approximately 75% endothelial coverage in rat lung scaffolds compared to native lungs.
• Demonstrated reduced vascular resistance and improved barrier function of the regenerated endothelium in vitro.
• Maintained patent vasculature for 3 days post-transplantation in rats and achieved perfusable lumens in human lung lobes.

Conclusions:

• Successful regeneration of functional pulmonary vasculature in decellularized lung scaffolds using iPSC-derived cells.
• Developed scalable methods for bioengineering lung vasculature, showing promise for future lung transplantation therapies.
• Regenerated vasculature exhibited improved function and patency, supporting its potential clinical applicability.