Heart transplant

Pig heart transplant saves heart patient

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Surgeons have succeeded in transplanting a genetically modified pig’s heart into a patient suffering from arrhythmia.
Photograph courtesy of University of Maryland School of Medicine
  • A team of surgeons from the University of Maryland School of Medicine recently transplanted a genetically modified pig heart into a 57-year-old man from Baltimore, MD.
  • The patient, who suffered from arrhythmia, was not a viable candidate for the list of heart transplants or an artificial heart pump.
  • The pig heart underwent 10 genetic modifications, including the deletion of four porcine genes and the addition of six human genes.
  • The surgical team hopes that the continued success of this transplant will provide a new way to help those on the organ donor list.
  • However, some members of the medical community question the ethical considerations of this type of transplant.

The faculty at the University of Maryland School of Medicine (UMSOM) recently performed a genetically engineered human heart transplant in a 57-year-old man from Baltimore, MD.

According to UMSOM, this procedure was the first time that a genetically modified animal heart replaced a human heart and was not automatically rejected by the patient’s body.

Dr. Bartley P. Griffith, director of the heart and lung transplant programs and Thomas E. and Alice Marie Hales Emeritus Professor of Transplant Surgery at UMSOM, was one of the surgeons who performed the transplant surgery.

He believes the transplant will provide new options for people in need of new organs and help solve the organ shortage crisis.

Xenotransplantation is the process of transplanting living organs, tissues or cells from a non-human animal into a human being.

The idea of ​​cross-species transplantation is not new. Research shows evidence of xenotransplantation as early as 17th century when the medical treatments included blood transfusions from non-human animals to humans.

More recently, NYU Langone Health announced that it had completed the second experimental transplant of a genetically modified pig kidney into a deceased patient kept alive on a ventilator. Scientists observed kidney function for 54 hours and reported signs of expected kidney function and no signs of rejection by the human host.

Dr. Muhammad M. Mohiuddin, professor of surgery and director of the cardiac xenotransplantation program at UMSOM, was also part of the surgical team. In 2016 he published research showing how a genetically modified pig’s heart could survive in a baboon’s abdomen for more than 2 years.

Dr. Mohiuddin and his team used genetically modified pigs to avoid stimulating organ rejection. They also developed an immunosuppressive drug procedure to ensure that the host body does not reject pig hearts.

Dr Griffin, Dr Mohiuddin and their team have reportedly spent the past 30 years refining surgical techniques for this transplant they performed earlier this month.

The patient, Mr. David Bennett, 57, of Baltimore, MD, agreed to the procedure after entering the hospital 2 months prior with an arrhythmia. An arrhythmia occurs when a person’s heart beats irregularly. In Mr Bennett’s case, his condition was life-threatening and he needed to be connected to a heart-lung bypass to stay alive.

Mr Bennett was also not a viable candidate for the heart transplant list, and his arrhythmia made him ineligible for an artificial heart pump.

Due to the urgent nature of her condition, on December 31, 2021, the Food and Drug Administration (FDA) gave the surgical team emergency clearance to perform the transplant.

The pig heart that the surgeons used for the transplant was genetically modified for xenotransplantation. Dr. Griffith explained to DTM how it worked.

“Genetically modified pig organs have been the focus of much xenotransplantation research, in part because of the physiological similarities between pigs, human and non-human primates,” Dr. Bennett said.

“The donor pig had 10 genetic changes, including the knockout (inactivation) of four porcine genes and the addition of six human genes.”

“Building on the GalSafe (KO alpha-Gal) platform, two other carbohydrate antigens were knocked out of pig Cmah and Beta-4-gal Genoa. To maintain a human-sized organ, the growth hormone receptor gene was also knocked out. Two human complement inhibitor genes (CD46 and ADF), two human anticoagulant genes (EPCR and Thrombomodulin) and two human immunomodulatory genes (CD47 and HO1) were inserted in a targeted manner into the genome of the donor pig.

Additionally, the surgical team used a new drug from Kiniksa Pharmaceuticals in combination with other anti-rejection drugs to help suppress Mr. Bennett’s immune system so he wouldn’t reject the pig heart.

Six days after the operation, news reports revealed that Mr Bennett’s recovery was continuing with no signs of his body rejecting the pig’s heart.

DTM asked Dr Griffith what the recovery process might look like for Mr Bennett. “As far as we know at this point, it’s very much like a human heart transplant in terms of rehabilitation and lifestyle,” Dr. Griffith explained. “He is on an anti-rejection drug regimen that includes an experimental drug. We do not know the full extent of side effects of this drug.

The UMSOM surgical team hopes that this transplant will positively affect the future use of xenotransplantation to help those who are currently waiting on the organ donor list.

According to the American Transplant Foundation, nearly 107,000 American citizens are currently waiting for lifesaving organ transplants. About 17 people die every day while waiting on the list.

“We hope this will pave the way, but it’s too early to tell,” Dr Griffith added. “The next step would be to study the use of these grafts in a clinical trial. We are in discussions with the FDA on what steps we need to take to start a clinical trial, but it will likely take a year or more due to the regulatory studies we would need to do first.

DTM also spoke with Dr. L. Syd M Johnson, philosopher, bioethicist, neuroethicist and associate professor at the Center for Bioethics and Humanities at Upstate Medical University, NY, about the ethical considerations of xenotransplantation.

Dr Johnson said that with xenotransplantation experimentation going on for almost 60 years with many failed attempts, it is too early to call this transplant a success.

According to Dr. Johnson, in the past, most xenotransplantation research focused on using organs from non-human primates because they are the closest genetic relatives of humans. However, this research was halted due to the unknown but potentially serious risks of virus transmission from other primates to humans.

“That risk still exists with pigs, both from viruses they are known to carry and transmit to humans and from possible, yet unknown, pathogens,” she added. “As we enter the third year of a deadly global pandemic caused by SARS-CoV-2, a zoonotic virus that has been found in many other animal species, the risks of zoonotic pathogens should be at the forefront. as we consider doing the xenotransplantation. .”

With the current interest in using pig organs for xenotransplantation, Dr Johnson said while some may argue that millions of pigs die each year for their meat, there is no real problem. ethical to use them for their organs.

“Pigs that are used for their organs are quite different from those that are killed for meat,” she explained. “They are genetically engineered in an effort to prevent rejection and eliminate some of the known retroviruses they carry.”

“These are pigs that will live their entire short lives in isolated, indoor, sterile facilities, subject to infection control measures, including artificial insemination and cesarean births. If pigs are used for multiple organs and tissues, they could be subject to prolonged damage including repeated surgeries, restraint and anesthesia events, painful procedures, tests and biopsies. Pigs are intelligent, social and emotionally complex animals, and their use as organ factories would violate our current best practices for animal care and welfare.

Rather than using xenotransplantation, Dr. Johnson urges the medical community to look for other alternatives to solve the problem of organ shortage.

“One is to prevent the need for transplants by developing better therapies for common diseases like diabetes, heart disease and hypertension that lead to organ damage,” she said.

“Another is to accelerate research into human-relevant alternatives, such as 3D bioprinting and growing human organs from stem cells. donors who may have chronic illnesses or who are older – is already underway and can make more organs available to people who need them Finally, we should use social engineering, rather than pigs from the bioengineering, to find better ways to encourage more humans to become organ donors.