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Stem cells may let transplant organs avoid rejection

Could stop immune system from attacking

Harvard Apparatus researcher Linghui Meng checked one step in the company’s process of creating artificial tracheas.

Joanne Rathe/Globe Staff

Harvard Apparatus researcher Linghui Meng checked one step in the company’s process of creating artificial tracheas.

An organ transplant offers a new lease on life but, as with any lease, there is important fine print:

Patients will need to take powerful drugs to suppress the body’s immune system and prevent it from attacking the new organ. So even if the transplant takes, patients can become seriously sick, and even die, because of minor illnesses that a fully functioning immune system would ward off easily.

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But a potential breakthrough is underway in Holliston, where a company called Harvard Apparatus Regenerative Technology is developing a system that dramatically reduces the risk of rejection and the need to suppress the immune system. The trick is that Harvard Apparatus infuses the transplant tissue with a patient’s own stem cells before surgery, fooling the body into believing the new organ is actually its own.

“When you have immunosuppressive drugs, it can be very nasty for the patient,” said Harvard Apparatus president David Green. “So it’s a huge step forward to be able to do any type of organ or tissue transplant without needing those drugs.”

What’s more, Harvard Apparatus
is working on synthetic tissue woven together with plastic fibers 100 times thinner than a human hair, which in some cases could eliminate the need for an organ donor.

The company has started with artificial tracheas and already has worked with a doctor from Sweden to implant six of its windpipes in patients, including one in the United States, under special exemptions because approval by the Food and Drug Administration and equivalent regulators in other countries is still several years off.

And the potential exists to perform similar transplants of more complex organs in the future. Though current technology cannot engineer synthetic hearts or lungs, it is plausible that surgeons could use a Harvard Apparatus bioreactor — a special device in which stem cells bond to new tissue — to replace a donor organ’s original cells with those of a transplant patient to prevent rejection.

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Dr. Harald C. Ott, principal investigator at the Ott Lab for Organ Engineering and Regeneration, in Cambridge, has used the bioreactor to perform organ transplants in rats. By pumping a detergent solution through an organ’s vascular system, it is possible to “wash off” the cells that identify it as belonging to a certain individual, leaving only its basic structure made of cartilage.

The stripped-down organ can then be placed in a bioreactor, which acts like a rotisserie, rotating it through a shallow pool of the patient’s bone marrow, containing stem cells. About half of the organ is submerged in the marrow at any given time, with additional marrow raining down from above. The marrow must be kept moving or the cells will die.

Ott believes the technique could be used on human hearts and lungs some day — probably not for 10 years — and said using a stripped-down donor organ as a “scaffold” for the stem cells of a transplant patient is more likely to succeed than efforts to grow whole organs from stem cells.

“I think the concept that we can take an embryonic stem cell and let it grow an organ in a dish is unrealistic,” Ott said. “I think the most promising concept is to take a scaffold that outlines the architecture and provides the environment that cells need, and then seed that scaffold with cells.”

Dr. Paolo Macchiarini used the scaffold of a donor trachea in 2008, when he performed the world’s first successful transplant of a regenerated trachea.

The landmark surgery caught the attention of Green, who e-mailed Macchiarini to ask whether he would be interested in licensing his technology to Harvard Apparatus, teaming up to create a bioreactor that could mechanize the 48-hour process of infusing a trachea with the cells of a transplant patient. Macchiarini agreed and added that he would also like to develop a synthetic trachea for future operations.

Building a synthetic trachea is a challenging exercise. The artificial windpipe must be rigid enough to avoid collapse yet supple enough to allow the neck to move freely. Originally, Macchiarini and Harvard Apparatus worked with a third-party company that produced plastic tissue in what Green described as a “Swiss cheese” pattern, but Macchiarini found the material difficult to graft in his first surgery in 2011, and Harvard Apparatus has made its own ever since.

Of the eight patients to receive regenerated tracheas, two died, but that was from health problems unrelated to their transplants.

One was the lone US patient, a 2-year-old girl from South Korea who was born without a windpipe.

Reached by phone in Stockholm, where he is a professor of regenerative surgery at the Karolinska Institute, Macchiarini said he is optimistic about future operations and stressed that viable synthetic organs will be the key to making transplants readily available.

“You have countries where the donation rate is very high, but there are other countries where you don’t have donations, so this could be a non-applicable technology,” said Macchiarini. “Our purpose as scientists is to make it available to everyone.”

Callum Borchers can be reached at callum.borchers@globe.com. Follow him on Twitter @callumborchers.

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