January 16, 2022

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The world first case: Pig heart transplanted to human

The world first case: Pig heart transplanted to human



 

The world first case: Pig heart transplanted to human. 


57-year-old David Bennett (David Bennett) completed a “experimental” heart transplant.

 

The heart was donated to a 1-year-old, 240-pound “genetically modified” pig.

 

Gene modification is the use of molecular biology techniques to remove the parts of animal genes that are prone to cause rejection, so that the transplanted animal organs can be compatible with the human body and survive for a long time.

 

The University of Maryland Medical Center (UMMC) , which performed the operation, officially announced that this is the world’s first human transplant of a transgenic pig heart.

 

On January 10, local time, the third day after surgery. Dr. Bartley Griffith , director of the UMMC Heart Transplant Program, said that Bennett still needs extracorporeal membrane oxygenation (ECMO) to replace part of the heart’s pumping function, but the overall condition is stable and good, and no ultrasonography has occurred. acute immune response.

 

The world first case: Pig heart transplanted to humanImage courtesy of University of Maryland Medical Center

 

“Either die or transplant the pig heart.” According to the UMMC press release, one day before the operation, Bennett said he was very aware of his state.

 

He said that he had received a pig valve transplant, and his favorite food was bacon. “This is a big gamble and my last choice for survival.” “But if possible, I still hope to transplant a human heart.”

 

Bennett suffered from end-stage heart failure due to complex genetic heart disease. In October 2020, his physical condition deteriorated suddenly and he was admitted to the hospital with a life-threatening arrhythmia.

 

His treatment plan was difficult to formulate. Several U.S. transplant centers, including UMMC, have assessed that Bennett’s arrhythmia is severe and unsuitable for implantation of an artificial heart. However, the basic situation is not eligible to enter the organ transplant waiting list.

 

 

The world first case: Pig heart transplanted to humanDavid Bennett (right) with the medical team. /University of Maryland Medical Center

 

 

Even if he is on the list, the chance that Bennett can wait for the organ in time is very low.

 

According to the United Network for Organ Sharing (UNOS) , about 41,354 Americans will receive organ transplants in 2021, including more than 3,800 heart transplants.

 

20:1 – This is the ratio of the number of patients worldwide in urgent need of organ transplants to the number of organs donated.

The “20” doesn’t include those patients who will be dragged on by drug maintenance but will eventually need a transplant.

 

About 17 people die every day waiting for organs, according to U.S. government data.

 

UMMC proposes “another possibility”: xenotransplantation, which uses animal organs to perform life-saving surgery.

 

The world first case: Pig heart transplanted to humanIn the process of preservation and transplantation, pig hearts must be perfused with special solutions to ensure viability. /University of Maryland Medical Center

 

 

According to the BBC, xenotransplantation can be traced back to 1682.

 

At the time, Dutch surgeon Job Janszoon van Meekeren said he used a fragment of a dog bone to repair a soldier’s skull. Upon hearing the news, the church asked him to take it out immediately, but found that the wound had healed.

 

The soldier’s follow-up is not yet known. But the exploration of xenotransplantation by medical scientists around the world has never stopped.

 

Since the 20th century, there have been many related surgical reports.

 

In 1905, France completed the world’s first human transplant of rabbit kidney slices. The recipient was a child with renal failure. 16 days after the operation, the patient died of a lung infection caused by rejection.

 

The following year, again in France, a pig’s kidney and a goat’s liver were transplanted into two female patients. Both died shortly after surgery from serious infections caused by taking immunosuppressive drugs.

 

In 1984 and 1992, doctors performed human transplants with baboon hearts and livers, respectively. The patient died of rejection within a few weeks after surgery.

 

In 2003, xenotransplantation entered a new phase. The American company Revivicor creatively carried out genetic modification on cloned pigs to cultivate the first generation of “medical pigs”. This was listed as one of the 100 major scientific discoveries of the year by the American “Discovery” magazine.

 

The name Revivicor may not be well-known, but its predecessor, PPL Therapeutics, a biotech company, made a name for itself – the creator of the world’s first cloned sheep, “Dolly.”

 

The world first case: Pig heart transplanted to human
A photo of a genetically modified pig provided by Revivicor in December 2020. The company did not state when the photos were taken. /AP

 

The question is: Why did Revivicor choose cloven-hoofed pigs for research, but gave up primates such as orangutans and baboons that are similar to humans in terms of species and anatomy?

 

The analysis of Revivicor pointed out that because “Second Senior Brother” is easy to use.

 

Pigs and humans are similar in food habits and metabolic levels, and their body temperature and heart rate are similar.

The “performance parameters” of some pig organs are also similar to those of humans. For example, a pig heart is about the same size as a human heart, with a similar distribution of pipes and power output.

 

In addition, primates have long generational gaps. In particular, orangutans and baboons have a generation of 10 years, one litter and one cub, and the cost of raising them is high. Pigs are raised in one litter and mature in more than a year, which is suitable for directional breeding and large-scale breeding.

 

More importantly, orangutans and baboons are “close relatives” of humans. Some viruses in its body, such as simian immunodeficiency virus, are easily transmitted to humans. When their organs are transplanted into humans, more powerful viruses may hatch.

 

Viruses in pigs are less likely to infect humans. In 2015, a research team from Harvard University in the United States used gene editing technology to knock out PERV (endogenous retrovirus) in the genome of pig populations , which is to clear the hidden danger of pig organ transplantation.

Previous studies have shown that pig cells containing PERV viroids run the risk of being activated and infecting human cells when incubated with human tissue.

 

Pigs are the best choice for xenotransplantation, which has become an international consensus.

At present, porcine heart valves and porcine pancreatic cells have successfully entered the human body. Pig skins are also used as temporary grafts for burn patients.

 

In December 2018, “Nature” published a blockbuster result saying that the team of Bruno Reichart (Bruno Reichart) of the Walter Brendel Center for Experimental Medicine in Munich, Germany , successfully transformed genetically modified pig hearts. transplanted into baboons. The longest survival time is 6 months.

 

 

Two years later, the journal Circulation published an article in Massachusetts General Hospital stating that pig hearts are expected to become human heart transplant donors.

 

The article predicts that humans may receive pig heart transplants as early as the end of 2021.

 

 

 

This prediction is awesome.

 

On December 31, 2021, the U.S. Food and Drug Administration (FDA) granted an “emergency authorization” for David Bennett’s experimental surgery through a “compassionate use” provision.

 

The pig heart donor used in the operation came from Revivicor.

 

The dedicated pig received 10 unique genetic modifications, UMMC said. Including the knockout of 3 genes to reduce the aggressive rejection response of the human immune system.

1 growth gene was knocked out to prevent the pig heart from continuing to grow after transplantation.

 

In addition, six human genes were edited and inserted into the genome of the donor pig. The goal is to make the pig’s organs more tolerant to the human immune system.

 

UMMC also uses an innovative drug to prevent rejection after organ transplants.

 

The genetically modified animal organ worked in Bennett’s body and was not immediately rejected, UMMC said. The outcome of this operation is likely to change the fate of many people around the world.

 

“We’ve never done anything like this in humans. I think we’ve given him (Bennett) a better treatment option than continuing to take medication,” said lead surgeon Dr. Bartley Griffiths. All risks and returns are unknown. “Whether he’ll live a day, a week, a month or a year, I don’t know.”

 


Group photo of the UMMC medical team. /AP

 

 

“This is a watershed event,” said Robert A Montgomery , director of the Transplant Institute at NYU Langone Medical Center .

 

In October 2021, with the consent of the patient’s family, Robert Montgomery also completed a xenotransplantation operation.

He transplanted the kidney of a genetically modified pig to a brain-dead end-stage renal disease patient.

 

This surgical procedure differs from the actual transplant. The pig kidney was not implanted in the patient, but was attached to the blood vessels of the thigh on the outside of the abdomen.

The surgical team explained that this is because in xenotransplantation, problems often occur at the anastomosis between human blood vessels and animal organs.

 

“The transplanted organ started functioning normally almost immediately,” Montgomery told The New York Times, and the fact that the organ works outside the body is a strong indicator that it will be very capable inside.

 


In October 2021, the world’s first transgenic pig kidney transplant was completed. /AP

 

 

In response to “when xenotransplantation will be widely promoted”, which is generally concerned by patients and the media, the UMMC team said that there are still many questions to be answered.

 

According to the opinion of the International Xenotransplantation Steering Committee, the prerequisite for xenotransplantation research to enter the clinic is that 60% of the animal experimental recipients survive for more than 3 months, and there are at least 10 consecutive transplant experiments.

 

The goal of the clinical trial is to permanently replace the original organ, and more than 50% of the recipients must survive longer than 6 months.

 

The next six months will be especially important for Bennett and the organ transplant community.

 

“If successful, genetically modified pigs could become a sustainable, renewable source of organs equivalent to the solar and wind energy supplied by the organs,” Montgomery told The New York Times.

 

At present, the production capacity and production license of these “medical pigs” have been guaranteed.

 

In December 2020, the US FDA issued a marketing license to Revivicor’s genetically modified pig GalSafe.

 

Unlike conventional pigs, GalSafe pigs are knocked out of the alpha-galactose molecule on the cell surface. This molecule is widely present on the cell surface of pigs, sheep, cattle and other “red meat” animals. Some people have allergic reactions to red meat, and they all depend on it.

 

In addition to making people allergic, alpha-galactose molecules are also one of the main causes of immune rejection. Because after evolution to primates, there is no galactose in the body.

 

According to the FDA, GalSafe pigs can be eaten directly or used to process and produce alpha-galactose-free medical products, such as the blood-thinning drug heparin.

 

What Revivicor hopes most with GalSafe pigs is the production of organs for xenotransplantation.

 

Time to move forward. In 2017, Smithfield Foods, the world’s largest pork producer, announced the formation of a new independent bioscience unit dedicated to raising “medical pigs”, hoping to form a pig organ production chain for human transplantation.

 

Allegedly, these pigs were delivered by caesarean section, separated from their mother pigs immediately after birth, and sent to ultra-clean pig houses for artificial rearing.

The pig house is sterile and non-toxic, and the breeding staff should bathe and change clothes before entering. All in all, it’s cleaner than some.

 

 

 

 

 

Reference:
1. In a medical first, a man with terminal heart disease gets a transplant of genetically modified pig heart. CNN
2. University of Maryland School of Medicine Faculty Scientists and Clinicians Perform Historic First Successful Transplant of Porcine Heart into Adult Human with End-Stage Heart Disease. University of Maryland School Of Medicine
3. US Surgeons Transplant Pig Heart Into Human Patient. Huffpost
4. A pig medical milestone. USA Today
5. US surgeons successfully test pig kidney transplant in human patient. CNN
6. Progress Toward Cardiac Xenotransplantation. Circulation. 2020;142:1389–1398. doi.org/10.1161/CIRCULATIONAHA.120.048186

The world first case: Pig heart transplanted to human. 

(source:internet, reference only)


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