Partial Decellularization Retains Cartilage Immune Privilege in Tissue Engineered Tracheal Grafts

Tracheal allografts have been used to reconstruct the human airway. However, the need for immunosuppression could ultimately limit their clinical translation. Partial decellularization (PD) has the potential to eliminate allograft immunogenicity while preserving donor cartilage. This study measures the effect of immunogenicity on tracheal allografts and PD on cartilage immunogenicity in partially decellularized tracheal grafts (PDTG).

Native and partial-decellularized trachea from C57BL/6 (control) and BALB/c (allograft, ATG) mice were transplanted orthotopically in C57BL/6 hosts (N = 3-10/group). At 10 days, 1 month, and 3 months, cartilage degradation, characterized as loss of chondrocytes and extracellular matrix (ECM) was assessed histologically. Acute and chronic rejection were measured with immunofluorescence CD4 and CD8 T lymphocyte infiltration.

Of 41 animals, 35 survived to endpoint and all grafts remained patent. Allografts exhibited cartilage degradation (loss of glycosaminoglycans, collagen, and chondrocytes) in 95.8% of animals versus 0% of animals that received syngeneic tracheal grafts (STG, control). In contrast to allografts, cartilage degradation was observed in 3.7% and 8.7% of partially decellularized grafts derived from syngeneic and allograft donors, respectively. ATG demonstrated more cartilage degradation and T-lymphocyte infiltration at each time point compared to STG and PDTG. T-cell infiltration peaked at 1 month. All grafts demonstrated more calcification (higher radiodensity) than the host (p < 0.05) in vivo.

In our mouse microsurgical model, we observed that in the absence of immunosuppression, tracheal allografts undergo cartilage degradation with associated T-cell infiltration. This phenomenon is not observed in grafts that underwent partial decellularization.

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