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From theory to therapy: Transplantation

Transplantation of modified organs using gene-editing technologies and rebuilding the skin with innovative tissue repair methods could save many lives and restore essential functions in a gentle way.

Over the past 50 years transplantation has become a successful worldwide medical practice, with advances including restoring sight in corneal blindness through corneal graft, transplantation of haematopoietic stem cells to cure congenital or acquired diseases, including some leukaemias, and the transplantation of a human heart valve. Xenotransplantation, animal to human, also has the potential to constitute an alternative to material of human origin and bridge the shortfall in human material for transplantation.

Last year a 57-year old man with a terminal heart disease in the USA became the first person ever to receive a transplant from a genetically modified pig heart.”

Last year a 57-year old man with a terminal heart disease in the USA became the first person ever to receive a transplant from a genetically modified pig heart. In the implanted heart three genes previously linked with organ rejection were “knocked out” of the donor pig, and six human genes linked with immune acceptance were inserted into the pig genome. A pig gene to prevent excessive growth of the pig heart tissue was also deleted. Although the patient died two months after the surgery (the medical team believes that his death was caused by his underlying heart disease), the transplantation is considered a real medical breakthrough and brings hope to the hundreds of thousands of people currently waiting for an organ transplant.

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Swedish medtech company Xvivo played a crucial part of this successful transplant. The company’s heart perfusion device, granted breakthrough device designation by the FDA in 2019, preserved the pig heart used in the surgery. The device, developed in collaboration with Stig Steen, professor of cardiothoracic surgery at Lund University and medical research company Igelösa Life Science, stores the donor heart in a solution at 8 C˚ that is pumped through the heart during transport.

To me, this is the ultimate proof that collaboration between scientists, clinicians and the industry is making the world a better place.”

“In the future where xenotransplants can help solve the donor organ shortage we are truly living our vision that nobody should die waiting for a new organ. We have always been in the forefront of organ technology and innovation. Therefore, it is nothing more than a true honor to be part of this first ever successful cardiac pig to human xenotransplant that could bring additional hope for patients on the waiting list. To me, this is the ultimate proof that collaboration between scientists, clinicians and the industry is making the world a better place,” stated Dag Andersson, CEO, Xvivo, after the transplantation.

 

Xvivo’s heart perfusion device. Photo: Xvivo

 

Tissue repair

Another breakthrough last year within this line of procedures was the development of a system that restores cells and maintains tissue integrity in a functional state after the loss of blood flow. The technology, OrganEx, developed by researchers at the Yale School of Medicine, could help extend the health of human organs during surgery and expand availability of donor organs for transplant (Andrijevic et al., Nature, 2022).

The device uses a mixture of the host’s blood and a protective fluid containing oxygen, a synthetic form of haemoglobin, electrolytes and compounds designed to protect cells and prevent blood clots.”

In studies the scientists were able to repair cells and organs in pigs one hour after the animals’ hearts stopped. Even at the genetic level, there were signs of tissue regeneration processes. The device uses a mixture of the host’s blood and a protective fluid containing oxygen, a synthetic form of haemoglobin, electrolytes and compounds designed to protect cells and prevent blood clots. These findings could lead to several opportunities in transplantology.

Post-transplant monitoring

Progress has also been made when it comes to post-transplant monitoring. Just a few weeks ago Swedish Devyser signed a collaboration and distribution agreement that gives Thermo Fisher Scientific exclusive rights to commercialize, under combined brands, Devyser’s post-transplant portfolio of next generation sequencing (NGS) products in North America and Europe.

Through close monitoring with chimerism testing, doctors can track engraftment and rejection in stem cell transplant patients and quickly detect any signs of relapse or lingering disease.”

Through close monitoring with chimerism testing, doctors can track engraftment and rejection in stem cell transplant patients and quickly detect any signs of relapse or lingering disease. The company’s kits are custom-built to help physicians create the best conditions for successful patient outcomes and to streamline lab operations with a fast, smooth workflow, they state.

The company recently won the Swecare Export Awards 2023 for its “revolutionary solutions, extensive export investment and focus on correct diagnosis for each patient in the shortest possible time”.

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