Scaffold in InBreath bioreactor prior to implantation. Image: HARTIn the 2nd century BC, Indian surgeon Sushruta used autografted skin transplantation in nose reconstruction, also known as rhinoplasty. This was the first reasonable account of organ transplantation recorded. The first successful human corneal transplant was performed in 1905 in the Czech Republic, and the first steps to skin transplantation occurred during World War I. The first successful kidney transplant happened in 1962 in the U.S.

Today, we can simply check off on the back of our license should we choose to donate our organs after death to save a life. However, one of the biggest problems with donor organ transplants (kidneys, hearts, lungs) is that a patient receiving the organ typically rejects the donor tissue. This causes recipients of the donor organ to take immunosuppressive drugs for the rest of their lives for survival.

Now this trend is changing.

It may seem far-fetched, or sound like science fiction, but it’s a real-life medical breakthrough. Laboratory-grown human organs and tracheas are now available for lifesaving transplants.

In 2008, a 30-year-old female received a new trachea that was grown using the InBreath bioreactor, created by Harvard Apparatus Regenerative Technology (HART), formerly a division of Harvard Bioscience, marking the first regenerative organ transplant surgery. It’s now five years later, and she is doing well.

“She has an excellent quality of life. She has a family and a job,” says David Green, CEO, HART, Holiston, Mass. “It’s really hard to imagine a better clinical outcome.”

That first patient was just the beginning for this technology. In July 2011, Andemariam Beyene was given two weeks to live. Beyene was a 36-year-old man who was suffering from late-stage trachea cancer that was deemed inoperable.

The average survival period for someone diagnosed with trachea cancer is only 10 months, and it is known as one of the most fatal types of cancer—more fatal than breast or prostate cancer. Typically these patients die today.

“It is the same thing with tracheal trauma,” says Green. “It isn’t usually the trauma or the physical damage to the trachea that kills them; what usually kills them is pneumonia. Once the trachea is damaged it becomes very difficult to keep pneumonia out of the infection site. So patients often die. What we have provided is a lifesaving procedure.”

But luckily for Beyene, Prof. Paolo Macchiarini of Karolinska Univ. Hospital and Karolinska Institutet and colleague Prof. Alexander Seifalian from Univ. College in London, England, agreed to operate on him at Karolinska Univ. Hospital in Huddinge, Stockholm. Seifalian had designed and built a nanocomposite tracheal scaffold, and Harvard Bioscience produced a specifically designed bioreactor used to seed the scaffold with Beyene’s own stem cells.

The culmination of decades of research, HART’s InBreath bioreactor allows surgeons to regenerate organs for transplant. The InBreath bioreactor is just one of three items needed to do so; a scaffold and a patient’s cells are also needed. With these three ingredients combined, the cells are seeded onto the scaffold, which is a porous plastic material that is flexible enough to move with the head and neck, but rigid enough to allow the airway to remain open. The plastic scaffold is seeded with the cells taken from the patient’s bone marrow, and the bioreactor is used to do that through a closed, sterile chamber in which the cells are incubated for two days prior to the surgery. Once it is ready, the surgeon will remove the old trachea that is damaged, usually due to trachea cancer or physical damage, and then the new one is stitched in.

For two days before the transplantation, Beyene’s own stem cells were grown on the scaffold inside  Harvard’s bioreactor. Because the cells used to regenerate the trachea were his own, there was no rejection of the transplant and no need for Beyene to take immunosuppressive drugs after.

Seeded scaffold. Image: HARTTwo and half years after surgery, Beyene is alive and well, says Green.

“There is no other technology doing this. We are the only ones,” says Green. And so far, eight other patients have also received similar stem cell transplants, and none took immunosuppressive drugs or antirejection drugs after the implantation. The reason for this: The technology uses the patient’s own cells.

Besides for trachea, there are no other organs the technology has generated for human transplant. However, according to Green, there has been recent research conducted by the Massachusetts General Hospital in Boston on animals with lung regeneration and transplant using the bioreactor.

The animal study was conducted in a similar way to that of the world-first regenerated organ transplant in 2008. “That was done by taking a donor trachea from someone who died in a road accident, just the same as a regular organ donor transplant,” says Green. “But the difference is that the cells on that donor scaffold were removed in a process called decellularization. And once the cells are removed, there is nothing for the patient’s body to reject. And then that donor scaffold, stripped of all its cells, is seeded with bone marrow taken from the patient. So the seeding is the same in all the cases; it is just the scaffold that is different.”

The approach is called decell, because one must decellularize the donor scaffold and then receullularize the scaffold with cells from the patient. That decell-recell approach is how the lung transplant was done. A lung was taken from a rat and stripped of cells. “What that does is leave behind a ghost lung, a white, translucent wall in the shape of a lung that has all the connective tissue and collagen left behind, but doesn’t have any cells left behind,” says Green. Then that scaffold is seeded with cells from a different rat and then implanted back into the rats.

What’s next for the technology? As eight patients have already been treated, this marks the end of the discovery phase and the technology is now moving into the clinical trial phase—the phase one needs to prove in a rigorous, statistically sound fashion that the procedure and technology work and are safe and effective for patients plagued with trachea cancer or trauma.

HART is just starting this process in both Europe and the U.S. When the company completes the process, they expect the ability to bring the therapy to all patients who need hope where hope may be lost.