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Surgeons in Sweden have successfully transplanted a fully synthetic, tissue-engineered organ—a trachea—into a man with late-stage tracheal cancer. The synthetic trachea was created entirely in the lab, using a scaffold built out of a porous polymer, and tissue grown from the patient’s own stem cells inside a bioreactor designed to protect the organ and promote cell growth.

The surgery was performed last month by Paolo Macchiarini at Karolinska University Hospital in Huddinge, Stockholm. The patient has now made a full recovery, and will be discharged from the hospital today.

The scaffolding for the trachea was built by a team led by Alexander Seifalian, professor of nanotechnology and regenerative medicine at University College London. Tissue was grown on top of the scaffold from the patient’s own stem cells using the “InBreath” bioreactor from Harvard Bioscience. The scaffold was seeded with a solution of stem cells taken from the patient’s bone marrow, and kept warm and sterile as the scaffold rotated inside the bioreactor while the cells grew into tissues. The entire process took about two weeks.

The transplant is a significant moment for regenerative medicine, says Arnold Kriegstein, director of the Broad Center of Regeneration Medicine and Stem Cell Research at University of California, San Francisco. “Finding ways for stem cells to be used to engineer replacement parts,” is exactly what regenerative medicine promises, Kriegstein says.

However, Kriegstein notes that a trachea is “relatively low-hanging fruit” because it is primarily a mechanical organ—a conduit for air. Building something as complex as a lung or a kidney would be far more challenging, he says.

Artificial organs would be superior to ordinary donor organs in several ways. They can be made to order more quickly than a donor organ can often be found; being grown from a patient’s own cells, they also do not require dangerous immunosuppressant drugs to prevent rejection.

Replacement organs have been grown, and implanted, in the past, using a patient’s cells and a donor organ stripped of its tissue, with the remaining cartilage to serve as a scaffold for tissue growth. In 2006, a team at the McGowan Institute for Regenerative Medicine in Pittsburgh successfully implanted lab-grown bladders in children with spina bifida. Synthetic scaffolding had been created previously, but it had not been used to replace a human organ.

To construct the trachea, Seifalian and his team used a polymer pitted with millions of tiny little holes to provide places for the patient’s stem cells to take root.

First, Seifalian and his team created a glass mold of the patient’s trachea from CT scans of the patient. Then, they cut strips of a polymer and wrapped them around the model to create the cartilage “rings” that give structural strength to the trachea. And they dipped the model into a liquid version of the same polymer, which had been mixed with salt. Finally, they washed the whole thing in a solution that dissolved the salts and caused the liquid polymer to congeal into a spongy form that resembles an organic trachea.

Once the trachea scaffold was built, living tissue was grown on top of it using Harvard Bioscience’s “InBreath” bioreactor—a shoebox-sized device in which the trachea was mounted “much in the way you’d mount a chicken on the rotisserie,” says David Green, president of Harvard Bioscience. A solution of stem cells from the patient’s bone marrow was poured onto the synthetic trachea, and the scaffolding was rotated while kept sterile and warm. The solution included chemicals meant to coax the cells to differentiate into the types of cells found in a trachea. It took about two days for tissues to form.

Building the scaffolding was slowed by this being a first-time effort, explains Seifalian. In future, he says, they could build a complete scaffold from CT scans in two days.

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Credit: Harvard Bioscience

Tagged: Biomedicine, regenerative medicine, transplant

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