A Yale University-led team of scientists reports that it has achieved an important first step in regenerating¹ fully² functional³ lung tissue that can exchange gas, which is the key role of the lungs. Their paper appears in the June 24 issue of Science Express. Lung disease accounts for（占比例） around 400,000 deaths each year in the United States. Lung tissue is difficult to regenerate⁴ because it does not generally repair or regenerate beyond the microscopic⁵（微观的） level. The only current way to replace damaged adult lung tissue is to perform lung transplantation, which is highly susceptible（易受……影响的） to organ rejection⁶ and infection and achieves only 10% to 20% survival at 10 years.

The Yale team's goal was to see if it was possible to successfully implant⁷ tissue-engineered lungs, cultured in vitro（在体外，在试管内） , that could serve the lung's primary function of exchanging oxygen and carbon dioxide. They took adult rat lungs and first removed their existing cellular⁸ components⁹, preserving the extracellular matrix（细胞外基质） and hierarchical（分层的） branching structures of the airways¹⁰ and vascular¹¹ system（血管系统） to use later as scaffolds（支架，脚手架） for the growth of new lung cells.

They then cultured a combination of lung-specific cells on the extracellular matrix, using a novel bioreactor designed to mimic¹² some aspects of the fetal（胎儿的） lung environment. Under the fetal-like conditions of the bioreactor, the cells repopulated the decellularized matrix with functional lung cells. When implanted into rats for short intervals¹³ of time (45-120 minutes), the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs.

Lead author Laura Niklason, M.D., Ph.D., professor and vice-chair of the Departments of Anesthesiology and Biomedical Engineering at Yale University and a member of Yale Medical Group, said, "We succeeded in engineering an implantable lung in our rat model that could efficiently¹⁴ exchange oxygen and carbon dioxide, and could oxygenate（氧化，充氧） hemoglobin（血红蛋白） in the blood. This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans."

The team found that the mechanical characteristics of the engineered lungs were similar to those of native tissues and, when implanted, were capable of participating in gas exchange. "Seeded and cultured epithelium（上皮细胞） displays remarkable¹⁵ hierarchical organization within the lung matrix, while seeded endothelial cells（内皮细胞） efficiently repopulate the lung vasculature（脉管系统） , Niklason said.

The Yale team says this is an important first step, but a great deal more research must be done to see if fully functional lungs can be regenerated¹⁶ in vitro, implanted and sustained in their functioning. Niklason says that for this technology to be applicable to patients, it is likely that years of research with adult stem cells will be needed to repopulate lung matrices and produce fully functional lungs.