U. MINNESOTA (US)—As a follow-up to the beating heart, researchers at the University of Minnesota have used a similar technique to create breathing lungs in the lab.

The process called whole organ decellularization is used to remove cells from the lungs of dead adult mice and implant healthy stem cells derived from unborn mice into the decellularized matrix, the natural framework of the lungs.

After about seven days in an incubator, the infused cells attached themselves to the matrix while breathing with the aid of a tiny, make-shift ventilator. The work is reported in the journal Tissue Engineering.

Potential benefits

Lead researcher Angela Panoskaltsis-Mortari, associate professor of pediatrics and pulmonary medicine, believes the “possibilities are endless” for using the system to increase the number of lungs needed for transplant into people with lung cancer and irreversible lung diseases.

One possibility she foresees may be removing lungs from a deceased person, decellularizing them, and seeding the remaining structure with patient-derived stem cells to reproduce and develop into lung cells—and then transplanting the new lungs into people with diseased lungs to give them a renewed lease on life.

Leading killer

Lung disease is the third leading killer of people in the United States, according to the American Lung Association. And, each year about 400,000 Americans die from lung diseases.

“Lung transplantation is usually the only option for patients with irreversible structural lung damage caused by cancer and chronic obstructive pulmonary diseases (COPD)—emphysema, idiopathic pulmonary fibrosis, primary pulmonary arterial hypertension, and cystic fibrosis,” Mortari says. “But major obstacles, such as not having enough donor lungs to transplant and chronic rejection, have limited the success of lung transplantation.”

The decellularization method
“While there is considerable scientific interest in developing cellular therapies for lung diseases, a primary obstacle has been finding a suitable way to evaluate young stem cells for their regenerative or reparative capacities,” Mortari says. “The lung matrix bioreactor system we developed can address that issue and provide a method for evaluation.”

The decellularization method used by Mortari and her colleagues essentially involved using nature’s platform to create bioartificial lungs. The method allowed them to remove the resident cells without damaging the intricate structure and scaffolding of the lungs.

Maintaining the natural scaffolding is essential Mortari says because scientists have not been able to replicate the framework of the lungs. The natural scaffolding of the lungs provides important cues to the cells that inform them to behave like lung cells.

Then they extracted young lung stem cells from unborn mice and injected them into the decellularized lung structure. About a week later, the new lung began to work, producing proteins normally expressed by healthy lungs.

The Mortari lab recently presented similar findings using induced pluripotent stem cells (iPS cells) at the American Thoracic Society’s annual international conference held in New Orleans. iPS cells are a source of stem cells that can be derived from one’s own cells from a healthy part of the body, and would not be subject to rejection after transplant.

This research project was funded with a grant from the National Institutes of Health.

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