Paolo Macchiarini (born August 22, 1958):2 is a thoracic surgeon and a former professor of Regenerative Medicine at Karolinska Institutet in Stockholm (Sweden). He is now being investigated for research fraud. Previously he was considered a pioneer in the field of regenerative medicine using both biological and synthetic scaffolds seeded with patients' own stem cells to regenerate trachea.:51 Macchiarini has been accused of research misconduct and unethically performing experimental surgeries, even on relatively healthy patients. Six of the eight patients who have received a synthetic trachea transplant have died. Also, an article in Vanity Fair has claimed that Macchiarini has made up some of his academic credentials on résumés. Similar accusations have been published in the Swedish newspaper Aftonbladet according to which Macchiarini's claim to have been a professor at universities in Hannover and Barcelona has turned out to be false. The secretary of the Nobel Committee for Physiology or Medicine, Urban Lendahl, resigned in February 2016, being involved in hiring Macchiarini to the Karolinska Institute in 2010. Macchiarini's employment by the Karolinska is slated to end in November 2016 following a decision by the institution not to renew his contract.
Claudia Castillo: First transplant using patient's stem cells
In June 2008, Macchiarini conducted the world's first transplant of a donated trachea colonized with the stem cells of the patient, Claudia Castillo. "After a severe collapse of her left lung in March, Castillo needed regular hospital visits to clear her airways and was unable to take care of her children." The only treatment left to her following conventional medicine "was a major operation to remove her left lung which carries a risk of complications and a high mortality rate." Macchiarini proposed tissue engineering.
A team from Spain, the UK and Italy, collaborated on the surgery, which took place at Spain's Hospital Clinic of Barcelona. They stripped the donated organ of its cells and MHC antigens (involved in helping the body recognize foreign tissues). They used the remaining structure as a scaffold for the patient's own cells, which were cultured onto it.
The operation was an immediate success. "The graft immediately provided the recipient with a functional airway, improved her quality of life, and had a normal appearance and mechanical properties at 4 months. The patient had no anti-donor antibodies and was not on immunosuppressive drugs." The latter aspect was a significant advantage, as immunosuppressive drugs can "increase the risks of infection, malignancy, cardiovascular disease and bone marrow suppression." "The technique raises the prospect of transplants for patients whose organs are damaged by cancer, who then cannot take the drugs as they increase the risk of cancer returning."
Martin Birchall, then Professor of Surgery at the University of Bristol, commented on the importance of the operation's success: “Surgeons can now start to see and understand the very real potential for adult stem cells and tissue engineering to radically improve their ability to treat patients with serious diseases. We believe this success has proved that we are on the verge of a new age in surgical care”.
Castillo was reported to be in good health six years after the surgery.
March 2010: Ciaran Finn-Lynch is the first child to receive stem cell organ treatment, and also had the "longest airway that has ever been replaced." He was 10 years old when an earlier transplanted trachea (with metal stents) started to cut into his aorta, the main blood vessel coming out of his heart. After several operations, there was still bleeding from the stents. With no other options in sight, the team leader thought of Macchiarini's earlier success with Castillo.
Macchiarini joined colleagues at London's Great Ormond Street Hospital during the operation, which was led by Martin Elliott, and included Martin Birchall of University College London. Macchiarini seeded the child's stem cells to the donated trachea and applied growth factor chemicals. He explained, "We told the cells to differentiate and transform naturally into the layers that make up the airway."
Due to the urgency of the child's condition, surgeons weren't able to wait for the patient's stem cells to develop into trachea cells in the lab. Martin Birchall said: "To minimise delays, we bypassed the usual process of growing cells in the laboratory over a period of weeks, and instead opted to grow the cells inside the body, in a similar manner to treatments currently being trialed with patients who have had heart attacks." Using this technique, "the boy's trachea was ready to be implanted in just four hours." The entire operation lasted nearly nine hours.
The operation was successful. On March 20, 2010, team leader Martin Elliott said, "The child is extremely well. He's breathing completely for himself and speaking, and he says it's easier for him to breathe than it has been for many years." After six months, his trachea looked almost normal, and his progress continued.
In April 2013, then 14-year-old Finn-Lynch was honoured with a Pontifical Hero Award for his courage, during the Second International Adult Stem Cell conference at the Vatican. He was the second person to receive the award.
Macchiarini believed that the implications for future treatments went beyond organ replacement, to the healing of damaged organs with stem cell therapy. "We need to change our philosophy…. The question is do we really need to transplant the entire organ and put the patient on immunosuppression, or can we stimulate stem cells to make it function again?" Martin Birchall said that more clinical trials were needed, but was hopeful that the technique could "allow not just highly specialized hospitals to carry out stem cell organ transplants."
Andemariam Teklesenbet Beyene: first synthetic trachea
On June 9, 2011 at Karolinska University Hospital in Stockholm, Sweden, doctors including Macchiarini implanted a synthetic windpipe built up with the patient's own stem cells, into a 36-year-old man with late-stage tracheal cancer. The synthetic windpipe was made at University College London, by Professor Alexander Seifalian.
The implanted trachea became loose and Beyene died in January 2014.
A video of Andemariam 1 year after the transplantation is available here.
According to information uncovered by the Swedish documentary "Dokument Inifrån: Experimenten" (Swedish: "Documents from the Inside: The Experiments") Andemariam went from suffering an increasingly terrible and eventually bloody cough to dying, intubated, in the hospital. At that point, determined by autopsy, 90% of the synthetic windpipe had come loose. He allegedly made several trips to see Macchiarini for his complications, and at one point had surgery again to have his synthetic windpipe replaced, but Macchiarini was notoriously difficult to get an appointment with. According to the autopsy, the old synthetic windpipe did not appear to have been replaced.
Christopher Lyles: first U.S. citizen to receive synthetic trachea
The second person in the world, and the first in the U.S., to receive a synthetic trachea engineered with the patient's own stem cells, was Christopher Lyles of Abingdon, Maryland. He had "exhausted the limited treatment options available in the U.S. for his tracheal cancer." Mr. Lyles was operated on in Stockholm, Sweden, in November 2011, and returned home to Baltimore in January 2012. "'I’m feeling good,' Mr. Lyles said in a telephone interview from his home, where he was playing with his 4-year-old daughter. 'I’m just thankful for a second chance at life.'" However, Mr. Lyles died in March 2012, nearly four months after the surgery.
Hannah Warren: first baby to receive synthetic trachea
Hannah Warren of Korea was born in August 2010 with an underdeveloped trachea. She survived for 2 years thanks to a tube inserted in a bronchus through the oesophagus and an aesophagus-broncus fistula. In April 2013, at the Children's Hospital of Illinois at OSF Saint Francis Medical Center (in a 9-hour procedure working with local pediatric surgeon Mark Holterman- the parents, a Newfoundland, Canada man and a South Korean woman living in her country), he gave a 3-inch long, bone marrow stem cell-cultured artificial trachea, or windpipe, to 2-year-old Hannah Warren, who had until then spent all her life in the Seoul National University Hospital in Seoul, South Korea, and was initially not expected to survive. She was the youngest patient yet to undergo that procedure, and only about 50,000 people in the world have her condition. Hannah died a few months later on July 6, 2013. Her family stated: "Her new trachea was performing well, but her lungs went from fairly good, to weak, to poor."
In two separate filings in June and August 2014 Macchiarini was accused of having falsified claims in his research by four former colleagues and co-authors. The Karolinska Institute appointed an external expert to review the charges, comparing the results reported to the medical record of the hospital. His investigation was presented in May 2015 finding Macchiarini guilty of research misconduct and that he had exagerated the outcome of his operations in six of the seven articles reviewed. After considering the findings and a lengthy rebuttal provided by Macchiarini the vice-chancellor of Karolinska Institute Anders Hamsten decided to clear Macchiarini of the allegations.
Related to the findings that emerged in the investigation Swedish MPA (Medical Products Agency) and the Health and Social Care Inspectorate decided to press charges for the three operations performed in Sweden. The charges against him, for which he is still under investigation, are manslaughter and bodily harm.
Professor Emeritus at Uppsala University Bengt Gerdin who the Karolinska Institute originally brought in to review the case expressed critique of the vice-chancellor treatment of the allegations, in an interview in Swedish television. These concerns were echoed by the chairman of the Karolinska Institute, Lars Leijonborg, and the chariman of the Swedish Medical Association, Heidi Stensmyren, calling for an independent investigation that would also look at how the issue was dealt with by the university management.
A story published by Vanity Fair has strongly suggested that Macchiarini has fabricated large parts of his academic resume. The article paints him as a serial fabulist, detailing an alleged courtship and marriage arrangements with a NBC News producer despite Macchiarini being married at the time. The Karolinska Institute is currently looking into the allegations in regards to Macchiarini's resume.
Sveriges Television investigative TV show Dokument inifrån aired a three-part series in January 2016 titled "Experimenten" where Macchiarini's work was investigated. The documentary shows Macchiarini continuing operations with the new method even after it showed little or no promise, exaggerating the health of his patients in articles as they died one by one. While Macchiarini admitted that the synthetic trachea did not work in the current state, he did not agree that trying it on several additional patients without further testing had been inappropriate. Allegations were also made that patients' medical conditions both before and after the operations, as reported in academic papers, did not match reality. Macchiarini also stated that the synthetic trachea had been tested on animals before using it on humans, something that could not be verified. Following the series, Karolinska Institute stated that they would investigate his work again.
^"Once doctors had a donor windpipe, scientists at Italy's University of Padua stripped off all its cells, leaving only a tube of connective tissue. Meanwhile, doctors at the [UK's] University of Bristol took a sample of Castillo's bone marrow from her hip. They used the bone marrow's stem cells to create millions of cartilage and tissue cells to cover and line the windpipe. Experts at the University of Milan [Italy] then used a device to put the new cartilage and tissue onto the windpipe. The new windpipe was transplanted into Castillo [at Spain's Hospital Clinic of Barcelona] in June.""Doctors give woman a new windpipe, using her own stem cells", The Associated Press, Daily News (New York), November 19, 2008.
^"Youngest Girl Given Bio-Engineered Windpipe Dies". nbcbayarea.com. Retrieved October 2, 2013. A nearly 3-year-old toddler who was the youngest person ever to receive a bio-engineered organ died Saturday in Illinois, surgeons involved in her treatment said.