Engineering Vasculature in Decellularized Lungs

Researchers here demonstrate the ability to regrow the blood vessel network in a decellularized lung, an important step in creating any sizable amount of engineered tissue. Decellularization is the process of stripping cells from donor tissue, leaving the intricate structure of the extracellular matrix and its chemical cues to guide cell growth. That matrix scaffold can be then be repopulated with a patient's cells to create an organ ready for transplant with minimal rejection risk. Since the scientific community still cannot recreate the full complexity of the extracellular matrix in artificial scaffolds, this remains the only way to create fully functional patient-matched organ tissue at the present time. Even so repopulation of decellularized organs has only been successfully carried out for a few organ and tissue types to date. It is a complicated process to deliver the right types of cells and coax them into recreating tissues correctly, especially when it comes to the all-important blood vessels that will supply the organ's cells:

Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol.

Using these methods we achieved ~75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens.

Link: http://dx.doi.org/10.1038/nbt.3354

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