Engineering Functional Vasculature in Decellularized Lungs Depends on Comprehensive Endothelial Cell Tropism.

Area of Science:

• Regenerative Medicine
• Vascular Biology
• Tissue Engineering

Background:

• Decellularized lungs offer a promising scaffold for tissue engineering, but functional vascularization remains a challenge.
• Effective re-endothelialization is critical for the success of bioengineered organs, particularly for pulmonary applications.

Purpose of the Study:

• To evaluate the recellularization potential of different endothelial cell types within decellularized lung scaffolds.
• To assess the site-specific tropism and functional characteristics of repopulated vascular segments.

Main Methods:

• Acellular mouse lung scaffolds were perfused with rat pulmonary microvascular endothelial progenitor cells (RMEPCs), pulmonary arterial endothelial cells (PAECs), or microvascular endothelial cells (MVECs).
• Pulsatile perfusion was maintained for 8 days, followed by histological analysis to assess cell distribution and endothelial function.

Main Results:

• PAECs and MVECs showed selective tropism for larger vessels and microvasculature, respectively.
• RMEPCs repopulated all vascular segments without site preference.
• RMEPC-derived endothelium exhibited functional markers including thrombomodulin activity, junctional gene expression, and barrier formation.

Conclusions:

• RMEPCs are a promising cell source for engineering vascularized lung scaffolds due to their broad tropism and functional endothelial characteristics.
• The identified RMEPC phenotype is valuable for advancing vascular organ engineering, regeneration, and repair strategies.