Porcine Lung Extracellular Matrix
Figure 1: Native and decellularized porcine lung tissue stained with H&E Masson’s Trichrome shows maintenance of tissue architecture and removal of cell debris and blood. Collagen type I fibers (in brown) are preserved, as are elastin fibers (dark purple), and fibronectin (brown) throughout the tissue after decellularization. Scale bar = 100μm.
Advanced lung diseases such as pulmonary fibrosis, cystic fibrosis, and emphysema are a leading cause of death in the United States. Although lung transplantation is a viable alternative in some cases, the scarcity of donor lungs and low survival rate limits the feasibility of this modality as a long-term therapy. To address this limitation and provide tissue analogs that have cellular constituents that are patient specific (thus eliminating the need for immune suppressants), the Niklason lab has developed an initial method to decellularize tissue while leaving a decellularized “scaffold” intact. The focus of my work is to extend these protocols to pig and human lung tissue and create a scaffold with an intact “matrix footprint” for the repopulation of patient specific cells. Towards this aim, we have developed a systematic decellularization technique that capitalizes on gentle detergents at low concentrations and physiological pHs. By using this protocol, we are able to maintain the global tissue architecture, key ECM components, mechanical composition and cell-seeding potential of decellularized lung tissue while effectively removing resident cellular material (Fig 1).
Acquiring a with intact matrix biologic cues scaffold using a repeatable, scalable protocol was essential to produce viable lung constructs. Ongoing experiments include optimization of recellularization techniques for tissue-engineered lungs (e.g. gas exchange, mechanical distention, surfactant production, etc), and assessing age and species-dependent aspects of acellular matrix.