How biotech will change the game

With the demand for organ transplants at an all-time high, it is no secret that we are currently in the midst of an organ shortage crisis. Fortunately, the biotech industry is working on innovative ways to solve this problem. In this article, we take a look at three promising techniques that could make up the future of organ transplants. 

Xenotransplantation: A fast-growing field in clinical trials shaping the future of organ transplants 

When David Bennet received a new heart in January 2022, there was something very unusual about the organ being transplanted into his body – instead of coming from a human donor, it was actually a genetically modified pig heart. Marking a major breakthrough, it was the first time that a genetically engineered pig heart had successfully been transplanted into a human being.

This procedure is known as xenotransplantation. It refers to the transplantation of living organs, tissues, or cells from one species to another, and is currently being touted as the potential key to solving the organ shortage crisis. The process involves genetically modifying an animal organ – pigs are currently thought to be the best source due to similarities in organ size and physiology – with human gene insertions and/or pig gene deletions to make the recipient’s immune system believe that the foreign transplant is its own tissue, before the organ is then transplanted into the patient.

Although many attempts have actually been made over the last few decades to transplant animal cells, tissues, and organs into humans, the advent of new gene editing techniques like CRISPR has brought xenotransplantation back into the spotlight. Now, scientists can address issues, such as virologic and immunologic hurdles, that have historically played a role in preventing advancements in animal-to-human transplants. 

The past year has seen two biotech companies working in the field make considerable progress, as the U.S. Food and Drug Administration (FDA) recently gave them the go-ahead to proceed with their xenotransplantation studies.

United Therapeutics receives FDA approval to proceed with first clinical trial for gene-edited pig kidneys

One of these is United Therapeutics, the parent company of Revivicor, which designed the pig heart with ten genetic changes that was transplanted into Bennet courtesy of the FDA’s “compassionate use” authorization, allowing experimental treatments for emergency cases; Bennet had end-stage heart failure, with no other options to save his life. 

Earlier this month, United Therapeutics announced that it had received the green light from the FDA to start the first clinical trial for gene-edited pig kidneys – a key milestone for xenotransplantation, laying the groundwork for how it could reach FDA approval. The company said the first transplant of its UKidney is slated for the middle of 2025, with a total of six patients with end-stage renal disease taking part in the initial stage of the clinical trial. 

eGensis performs first genetically engineered organ transplant in compassionate use study

Another company making progress in xenotransplantation is eGenesis, with a platform that modifies the genome to reduce the molecular incompatibilities driving organ rejection and to address viral transmission risk. “These edits included knock out of three genes involved in the synthesis of glycan antigens that contribute to acute organ rejection, insertion of seven human genes to promote long-term organ compatibility and function, and inactivation of the endogenous retrovirus embedded in the porcine genome,” explained Curtis in a previous interview with Labiotech. 

In December 2024, eGenesis received approval for a three-patient kidney transplant study under compassionate use. The first transplant was performed on January 25 at Massachusetts General Hospital on a 66-year-old patient called Tim Andrews, who had end-stage renal disease. He received a pig kidney with 69 gene edits. After the procedure, Andrews was able to skip dialysis for the first time in more than two years. 

The next two transplants for eGenesis’ study will happen in July and October this year. 

Unfortunately, Bennet and several other patients previously transplanted with engineered pig organs did not survive, proving that there is still much to be learned about xenotransplantation, and there will likely be a long road ahead before any sort of FDA approval. 

Now, we will just have to wait and see whether Andrews and the upcoming transplant patients in eGenesis’ study and United Therapeutics’ clinical trial will react well to receiving their modified organs. 

3D bioprinting: Creating new organs with no need for donors

Bioprinting human organs using specialized 3D printers is set to be a very promising technique in the future of organ transplants. Unlike traditional 3D printing, which often uses plastics and metals, the aim of bioprinting is to fabricate living, functional tissue that is compatible with the human body using bio-ink. Generally, bio-ink is composed of cultured cells paired with biopolymer hydrogels, which help construct structures of organs and protect living cells during the printing process.

This process of bioprinting begins with creating a digital model, often obtained from MRI or CT scans of real organs. This model guides the bioprinter and, once the design is set, the bio-ink is deposited layer by layer, with each layer being solidified, either through cooling or chemical cross-linking. 

Transplanting organs with the use of 3D bioprinting is not necessarily a new technique; a breakthrough moment came in the early 2000s when Luke Massella, a patient with spina bifida, was successfully given a 3D bioprinted bladder made from his own cells. More recently, in a world-first, an ear was implanted on a 20-year-old woman born without one, produced by 3DBio Therapeutics from a 3D bioprinter using the woman’s own cartilage cells. And just last year, a recovering thyroid cancer patient also received a 3D-printed windpipe transplant.

Even though these procedures were seen as incredible breakthroughs in 3D bioprinting, the idea of printing a lung or heart to transplant into someone is a whole new ball game. As Didarul Bhuiyan, a biomaterial and tissue engineering scientist at West Pharmaceutical Services, said in an article for Built In, we are “far away” from transplanting complex, life-sized 3D-printed organs into humans, and the general consensus is that this will not happen for another 20 to 30 years. 

However, progress in this area is definitely speeding up, and there is some notable research taking place. For example, United Therapeutics Corporation has 3D printed a human lung scaffold with 4,000 kilometers of capillaries and 200 million alveoli that are capable of oxygen exchange in animal models, which is a significant step toward developing transplantable human lungs to be cleared for human trials in the next few years. Meanwhile, researchers at Tel Aviv University have produced a 3D-printed “rabbit-sized” heart with cells, chambers, the major blood vessels, and a heartbeat. 

In August last year, there was also news of a new 3D bioprinting method developed by a team of scientists from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Wyss Institute for Biologically Inspired Engineering. This method enables the printing of vascular networks that consist of interconnected blood vessels possessing a distinct “shell” of smooth muscle cells and endothelial cells surrounding a hollow “core” through which fluid can flow, embedded inside a human cardiac tissue. The vascular architecture here closely mimics that of naturally occurring blood vessels, signaling significant progress toward being able to manufacture implantable human organs. 

According to Grand View Research, the global 3D bioprinting market size, which was $2 billion in 2022, is expected to grow at a compound annual growth rate (CAGR) of 12.5% from 2023 to 2030, with this growth being attributed to the limited number of organ donors, as well as an increasingly aging population with chronic respiratory diseases.

Although we may still be a couple of decades away from seeing the approval of the first 3D bioprinted organ, it is fair to say that it could be a key area in the future of organ transplants. 

Repairing and cloning organs with stem cell technology

Stem cells have the ability to adapt and regenerate into different cell types in the body, meaning they can potentially be used to replace tissues damaged by disease. It is hoped that this might someday help doctors eliminate the need for transplants entirely, as well as the anti-rejection drugs used in transplantation.

Studies on mice are currently underway in the area of stem cells and transplantation, whereby immune organs are being grown in mice from lab-created cells. Additionally, cloning new organs from stem cells is another way that stem cells can aid people waiting for donor organs. Cloning is the act of reprogramming a cell by replacing its nucleus with that of another cell so it becomes the genetic equivalent of the original. 

Another approach that uses stem cell technology is developing human organs in animals. The Stanford School of Medicine and their collaborators conducted a study on this in 2022 to try and show that the idea was feasible. For this, it would be necessary to demonstrate that human stem cells could survive within the early embryo of an animal, which acts as a sort of biological incubator.

As laws in the U.S. carefully prohibit the option of experimenting with chimeras (a mixture of two genetically different cells) between humans and primates, the team at Stanford turned to the cells of non-human primates to act as a proxy, using chimpanzee cells. After the more robust stem cells were combined with the embryo of a rhesus macaque, the implanted cells were still alive two days later. Although a small feat, Michael Snyder, professor and chair of genetics at Stanford, said in an article that they “were able to show that the cells survive, replicate, and grow”, adding that these improved stem cells are going to be an essential part of their model and research.

The idea of using stem cell technology to solve the organ shortage crisis is still in the very early stages compared to xenotransplantation and 3D bioprinting. This is because research in stem cell medical technology is actually still in the infant stages and results are not expected for at least ten years. But, as stem cell research advances, it could become a promising solution that could play a big part in the future of organ transplants.

The future of organ transplants: New approaches fueled by a need to solve the organ shortage crisis 

Current statistics show that there are 104,799 people in the U.S. in need of a life-saving organ transplant – 17 of whom are likely to die today waiting for their transplant. The sheer number of people on the waiting list can be attributed to the ongoing organ shortage crisis, not just in the U.S., but on a global scale. 

Apart from the solutions that the biotech industry is working on, experts are also looking at other ways to improve the outlook for organ transplants. This includes helping transplants last longer by keeping patients healthier, identifying organ failure earlier, and enabling more donated organs to be safely used, as organ-perfusion systems enable donated organs such as lungs, hearts, kidneys, and livers to remain viable outside the body for a longer period of time so that they can be used, as well as allowing surgeons to restore organs that would otherwise not be safe for transplantation.

Unfortunately, many of these solutions, including xenotransplantation, 3D bioprinting, and stem cell technology, are a very long way away from being approved. 

However, the promise they hold in eventually solving the organ shortage crisis is undeniable. And, as technology progresses even further, perhaps the biotech industry can come up with even more solutions, ensuring that in a few years’ time, organ shortages will be a thing of the past.

New technologies related to organ transplants