A New Day Dawns in Regenerative Medicine

David Green, President of Harvard Bioscience, Inc.

After many rounds of aggressive chemotherapy and radiation, the 36-year old father and doctoral student still had a golf-ball sized tumor in his windpipe in May 2011.

Andemariam Beyene’s physicians told him his fate was sealed after multiple surgeons concluded that nothing further could be done for him. He almost went home to die in Eritrea, his homeland in East Africa.

Then Dr. Paolo Macchiarini of Italy agreed to one last life-saving measure -- the surgical implant of a new trachea constructed from the patient’s own adult stem cells grown on a synthetic tubular matrix known as a “scaffold.”

The scaffold for the custom-made windpipe was constructed using nanotechnology that could replicate the exact structure of the patient’s trachea using three-dimensional CAT scans. The porous tubing was then bathed -- both inside and outside -- in stem cells derived from his bone marrow. This process took just a matter of days prior to the 14-hour, life-saving operation in Sweden on June 9, 2011.

Thanks to the InBreath Bioreactor, a kind of biological rotisserie grill in which the scaffolding was basted with stem cells that successfully grew into living tissue, Beyene is now healthy roughly a year after his original death sentence.

David Green, president of Harvard Bioscience, Inc., which engineered the bioreactor, says: “The most exciting thing about this development is that we saved a human life. Our InBreath Bioreactor played a pivotal role in the construction of this patient’s new trachea.”

He notes that thousands of patients each year could benefit from this innovation because of emergency crises involving their trachea. “Many of these patients cannot be helped with traditional medical approaches, and there is only about a five percent five year survival rate for those with tracheal cancer,” he says.

Green adds that with this innovation in regenerative medicine, patients will not have to wait months for a tracheal donor transplant, nor tolerate the risks of rejection associated with donor organs. They also can avoid the complications and expenses associated with immuno-suppressive drugs.

That could potentially save a few thousand lives each year, while adding millions of dollars in new revenue for Harvard Bioscience per year.

Furthermore, Green says that “the InBreath Bioreactor could eventually be used for other hollow, tubular organs, such as the esophagus.”

“Critical care problems with the esophagus are far more common than tracheal issues,” he adds, which could translate to an even greater demand for the InBreath Bioreactor, in large part because of the far more numerous esophageal cancer cases reported globally.

It is even possible that this regenerative medicine innovation could offer hope one day to the millions of people with failing hearts and lungs, as those organs similarly consist of hollow or partly hollow structures that could be recreated in much the same way.

“Living cells have already been differentiated on scaffoldings for lung replacements in rats,” Green notes, adding that “it is a matter of when, not if, this technology will be used to create other human organs with regenerative medicine.”

For now, the scaffolds bathed in stem cells are only for research and investigative use, subject to local investigational device regulations. Green says that “the next step is more formal trials and then marketing.”

He explains that the bioreactor is designed to be the perfect rotisserie for growing natural tissue onto a scaffold because it is steadily oxygenated, kept at 98.6 degrees, and produces exactly the right level of shear stress from liquid stem cells running down the inside and outside of the scaffold, imitating the natural environment of the trachea.

The bioreactor’s rotating action thus stimulates the bone marrow cells to become tracheal tissue.

Furthermore, the bioreactor is designed to achieve the constant maintenance of sterility and the compliance with other criteria associated with well-defined “Good Laboratory Practice” in the medical device field.

Green acknowledges that another patient who received a tracheal implant in the U.S. created from the same experimental approach, recently died from pneumonia, but that occurred three and a half months after a successful implant operation in November 2011.

Harvard Bioscience’s latest foray into regenerative medicine builds upon a history of success in its mission to develop and market products used to advance both life science research and regenerative medicine. Already, the company is well known for its other products, such as syringe pumps, spectrophotometers, ventilators and electroporation products used in life science research.

Green says it is an intellectually challenging business in a fast-advancing field with many critical speed demands, and thus, it demands strong legal support. “I need my lawyers to know the law [and]... how it applies to my business, and I need them to be responsive,” he adds, noting that “sometimes I need something big, I need it today, and it may be short notice, but there is just no way around it.”

He credits Burns & Levinson attorneys Joe Volman and Chad Porter for their timely work “on many complex legal tasks involving corporate governance issues, SEC filings, financing projects and major transactions.” Green concludes that, regardless of the complexity, “they get things done and they give us that level of service we require.”

- John O. Cunningham, freelance writer/editor

The scaffold prior to seeding.

Bone marrow stem cells being seeded onto the saffold in the bioreactor.

Two days later the seeded scaffold immediately prior to implant in Mr. Beyene.