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February 21, 2024

Scaffolding organs is new approach to transplants

By AZWAD SABIK | October 11, 2012

In 2010, doctors diagnosed Andemariam Beyene, a man from Eritrea, with a tumor growing in his windpipe and determined his odds of survival to be slim. Its growth unhindered by both radiation therapy and surgery, the tumor appeared to be unmanageable.

The tumor was. Yet, the windpipe was not.

Upon consultation with surgeon Paolo Macchiarini of the Karolinska Institute in Sweden, it was decided that Beyene would be one of the first to undergo a transplant procedure that might give him a chance at beating the cancerous growth. His entire windpipe would be surgically removed and replaced with another.

The windpipe would be custom made, sized to Beyene’s  chest, and nearly indistinguishable from the original version in terms of its function and identity as his immune system would see it. However, neither Macchiarini nor anyone at his lab would make the organ — rather, Macchiarini hoped Beyene’s own body would handle the task, with only a little help from Macchiarini’s team.

Macchiarini’s lab, which specializes in tissue engineering, had been looking into alternative approaches to the work in their field. Taking cues from nature, the researchers focused on the fact that when an organ is stripped of its cells, a conglomeration of proteins called the extracellular matrix remains. The matrix defines the organ’s overall shape, and functions mainly to hold the surrounding cells in place.

The researchers believed that if they could create a substitute for this organ “scaffold” and cover it with cells specific to the organ, they could implant their creation within a patient and it would be accepted by the patient’s body.

In Beyene’s case, this method was a success. A polymer scaffold was created for a replacement windpipe at University College London utilizing data from scans of his own windpipe, and then Macchiarini’s lab used stem cells from Beyene’s bone marrow to cover the scaffold.

The stem cells, which have the unique capability of changing into any other cell in the human body upon proper stimulation, played a key role in the acceptance of the organ by Beyene’s body. After preparation in a nutrient solution, the organ was surgically placed within his body, and the wait was on.

After his surgery, Beyene had constant checkups with Macchiarini’s team to verify the proper function of his windpipe. The checkups revealed that the cells lining the inside of the windpipe had been replaced with ones specialized for that specific location, allowing mucus to form within the windpipe. The mucus can trap unwanted particles, preventing them from entering his body and causing infection, just as the cells of his original windpipe would have.

On top of that, blood vessels had begun forming around the cells so that the rest of the body could provide nutrients to support the windpipe. In short, the stem cells had served their purpose.

By minimizing outside intervention and simply providing the scaffold, Macchiarini had successfully coaxed Beyene’s body into regenerating itself.

Over a year later, Beyene is alive and well, able to breathe and live in relative peace thanks to this procedure. With a brand new windpipe, the issue of cancer no longer holds worry; with the use of Beyene’s stem cells to create the windpipe, there is promise of its continued function. The results give hope for procedures similar to his in the future.

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