Engineered organ developer Harvard Apparatus Regenerative Technology has done all it can to disassociate itself from the surgeon Paolo Macchiarini. The Holliston, MA-based company is now known as Biostage (NASDAQ: BSTG), uses a different technology, is led by a different management team, and no longer helps Macchiarini perform the surgeries that led to the company’s founding in the first place.
That’s a good thing, because the controversy for Macchiarini, who had been a world-renowned surgeon and stem cell scientist, continues to grow.
The Associated Press reported today that Macchiarini faces preliminary charges of involuntary manslaughter in Sweden related to two patients who died after surgeries to implant artificial tracheas to replace their damaged windpipes in 2011 and 2013. Macchiarini has denied the allegations, according to the AP, but this is the latest round of controversy for the surgeon whose work led to the formation of HART, now Biostage, three years ago.
Almost 10 years ago, former Harvard Bioscience CEO David Green read in the peer-reviewed journal The Lancet that a team led by Macchiarini (then a surgeon at Hospital Clinic in Barcelona, Spain and later the Karolinska Institute in Sweden) had prepared a new trachea for a woman with the help of a new type of bioreactor—a device that could keep cells sterile and alive long enough to grow into and around a scaffold. Macchiarini was heralded for performing the first such surgeries, and the work intrigued Green. He e-mailed Macchiarini about the work and wound up licensing the bioreactor technology from two of Macchiarini’s colleagues and brought the device in-house, looking for ways to refine it for commercial use.
That concept ultimately led Harvard Bioscience to create and spin out HART, a company focused on developing a line of replacement organs that incorporate a patient’s own cells. Green left Harvard Bioscience to run it; Xconomy profiled the transition, and Green’s plan for the company, in early 2014.
Harvard Bioscience, and later HART, provided bioreactors and scaffolds to Macchiarini’s labs for research and several “compassionate use” surgeries, which are granted for gravely ill patients with no other options. In return, Macchiarini was to provide data to help the development of HART’s own devices, which were still in preclinical testing. But he wasn’t employed by, affiliated with, or paid by the company, according to regulatory filings.
In 2014, however, HART cut ties with Macchiarini. In its latest annual report filed in March, the company said that the work being done overseas by Macchiarini “would provide less meaningful product development data” than what it was doing in its own labs. And since that time, Macchiarini’s work has come into question. He was the subject of at least two investigations at the Karolinska Institute, which challenged claims he’d made publicly and in peer-reviewed journals about surgeries he’d performed with HART products. Macchiarini was initially cleared of wrongdoing, but was dismissed from Karolinska earlier this year. That was after the release of a documentary series on Swedish television called The Experiments, which as Science Magazine reported here, suggested that a patient in Russia who could have lived a long life died after getting one of his artificial tracheas. (Here’s more in Vanity Fair on some of the controversy surrounding Macchiarini.)
HART, meanwhile, wiped the slate clean. It hired Saverio LaFrancesca as chief medical officer in 2014 and shortly thereafter scrapped the windpipes being used in Macchiarini’s surgeries in favor of a new technology it calls “Cellframe” and “Cellspan.” A regulatory filing shows that the old technology was causing an “unfavorable inflammatory response” in animals, meaning more testing and development was needed before the company could begin testing the technology.
Green resigned as CEO in April 2015 (he remains on the board), and the company changed its name to Biostage at the end of March this year. It asserts that it has made “dramatic improvements” with the new technology, which uses different materials and stem cell sources than before. (Twin Cities Business has more on that technology here.)
“We believe that prior statements by Dr. Macchiarini or others regarding the patients whose surgeries utilized our HART bioreactor or HART-Trachea scaffold, or such products, are not pertinent to our Cellframe technology or Cellspan products, or their respective future development,” the company said in its annual report.
As with the old technology, Cellframe and Cellspan have yet to be tested in human clinical trials—much has yet to be proven about their safety and effectiveness. Biostage aims to file papers later this year to begin those tests—likely to be trials testing the technology in patients whose windpipes were damaged by cancer, injury, or infection. Biostage is now working with the Mayo Clinic, not Macchiarini, on its research.