Researchers from the Vermont Lung Center and the Biodesign Institute at Arizona State University (ASU) are working on a new technique to develop viable lung tissue suitable for transplantation that could provide a virtually limitless supply of donor lung tissue while avoiding the host rejection that has long plagued organ transplantation. For patients suffering from severe pulmonary diseases, including emphysema, lung cancer, or fibrosis, such transplants of healthy lung tissue may offer the best chance of survival.

While some biological structures (including bladder and skin) may be grown in the laboratory, building a complex organ like a lung from scratch is outside the realm of current medical technologies. The method under study instead involves new techniques of tissue engineering. An organ extracted from a cadaver is chemically stripped of cells—a process known as decellularization—leaving behind a delicate architecture of the extracellular matrix. This scaffold is then recellularized—that is, repopulated using stem cells drawn from the intended transplant recipient.

Different types of stem cells are being investigated in this study for the successful repopulation of the decellularized lung scaffolds. These cell types include pluripotent and multipotent stem cells. Pluripotent cells have the ability to form virtually any cell type in the body, including cardiac, muscle, neuron, and the variety of cell types making up a functioning lung. While multipotent stem cells are more limited than pluripotent stem cells, they are easier to obtain from patients and involve less downstream risks.

The working hypothesis of this study is that when stem cells are applied to the decellularized lung scaffolding, they take up residence throughout the structure, differentiating into the appropriate tissue and vasculature of a normal lung. It is believed that subtle chemical as well as mechanical forces direct this metamorphosis.

This process of stem cell differentiation and rebuilding is assisted by placing the cells in a rotating wall bioreactor—a device that gently circulates fluid and oxygen through the cells in such a way as to mimic conditions during fetal development. The researchers hypothesize that the decellularized scaffolding subjected to this environment will help guide the stem cells adhering to this template to multiply and mature into the cell types essential for a functioning lung. Because the replacement organ is constructed with the recipient’s own cells, issues of immune rejection are minimal.

As the lungs under study are recellularized, they can be carefully evaluated in terms of biomechanics, vascular perfusion and normal lung phenotype, including the production of surfactants.

The technique is being developed under a $3.4 million grant from the National Institutes of Health. In addition, the project is a recipient of the 2010 ASU/Mayo Clinic Seed Grant program.

Source: Arizona State University