Both Leathan (L) and Godfrey (R) have aplastic anaemia, which can treated with a stem cell donation. Leathan received stem cells from his twin sister, who is a perfect match. But Godfrey must travels from KwaMhlanga to Pretoria for life-sustaining blood transfusions.
When aplastic anaemia struck two young South Africans, their fates diverged dramatically. While one received a life-saving stem cell transplant, the other continues to fight every day. The rare blood disease affects fewer than six people per million, but for Leathan and Godfrey, the statistics became deeply personal.
Understanding Aplastic Anaemia: When Hope Meets Science
Aplastic anaemia is a devastating condition where the bone marrow fails to produce sufficient blood cells, leaving patients vulnerable to infections, bleeding, and severe anaemia. Given this rare disease’s high mortality rates, prompt recognition and immediate action are critical for survival. “The challenge with aplastic anaemia is that early symptoms can be subtle,” explains Dr Gugulethu Jali, a Clinical Haematologist and Haematopathologist at the Department of Health Kwa-Zulu Natal. “However, advances in treatment, particularly hematopoietic stem cell transplantation (HSCT), have transformed the prognosis, with survival rates now exceeding 80% when matched donors are found.”
Leathan’s Journey: From Crisis to Recovery
Seventeen-year-old Leathan had his whole life mapped out. The passionate soccer player dreamed of becoming a criminal lawyer, balancing his love for the game with serious academic ambitions. But subtle symptoms began to appear, including weight loss and nosebleeds that seemed minor at first.
When he suddenly collapsed at home, his family rushed him to hospital where doctors discovered his blood levels were critically low. Tests revealed that his bone marrow had completely stopped producing blood cells. Without immediate intervention, he would need blood transfusions and platelets for the rest of his life.
But Leathan had something that changes everything in aplastic anaemia cases: a perfect genetic match. His twin sister, without hesitation, donated her stem cells , giving her brother the ultimate gift of life.
Today, Leathan represents the success story that medical advances have made possible. Since the transplant, he has not needed further transfusions, and his blood counts are steadily stabilising. However, he may still need additional stem cell support to fully restore his health.
Currently, he’s on the path back to his soccer dreams and law school aspirations, a living example of what’s achievable when the right match is found.
Godfrey’s Battle: The Same Disease, Different Circumstances
While Leathan’s recovery shows what’s possible, eleven-year-old Godfrey from KwaMhlanga, Mpumalanga, is still living with the daily reality of aplastic anaemia. Like Leathan, Godfrey was once full of energy and loved soccer.
Then the familiar pattern began to emerge: Godfrey started moving more slowly, struggling with everyday tasks that once came easily. When uncontrollable bleeding began, his family knew something was seriously wrong. After a long diagnostic journey that began in 2019, Godfrey received the same diagnosis Leathan had faced: aplastic anaemia.
Unlike Leathan, Godfrey doesn’t have a twin sister who’s a perfect match. Instead, every month, he travels from KwaMhlanga to Pretoria for life-sustaining blood transfusions. The physical and emotional toll has been devastating. He was unable to pass Grade 5 last year, not because he lacks ability, but because fighting for your life leaves little energy for schoolwork.
Your Role in Changing Godfrey’s Story
For Godfrey to follow the same path as Leathan, he needs his genetic match. That person could be you.
Compatible donors are often found within similar ethnic backgrounds, making diversity in donor registries crucial for patients like Godfrey. If you’re between 17 and 55 and in good health, registering as a stem cell donor takes minutes and costs nothing. Register today at https://www.dkms-africa.org/save-lives.
Research in the Journal of Hepatology demonstrates that genetically engineered porcine livers can support key hepatic functions in humans
A landmark study in the Journal of Hepatology reports the world’s first auxiliary liver xenotransplant from a genetically engineered pig to a living human recipient. (Credit: Journal of Hepatology / Zhang et al.)
An important new study in the Journal of Hepatology, published by Elsevier, reports the world’s first auxiliary liver xenotransplant from a genetically engineered pig to a living human recipient. The patient survived for 171 days, offering proof-of-concept that genetically modified porcine livers can support key metabolic and synthetic functions in humans, while also underscoring the complications that currently limit long-term outcomes.
According to the World Health Organization, thousands of patients die every year while waiting for organ transplants due to the limited supply of human organs. In China alone, hundreds of thousands experience liver failure annually, yet only around 6000 people received a liver transplant in 2022. This pioneering case offers a potential new avenue to bridge the gap between organ demand and availability.
The case involved a 71-year-old man with hepatitis B-related cirrhosis and hepatocellular carcinoma who was not eligible for resection or human liver transplantation. Surgeons implanted an auxiliary graft from a genetically modified Diannan miniature pig with 10 gene edits, including xenoantigen knockouts and human transgenes to enhance immune and coagulation compatibility.
For the first month after surgery, the graft functioned effectively, producing bile and synthesising coagulation factors, with no evidence of hyperacute or acute rejection. However, on day 38, the graft was removed following the development of xenotransplantation-associated thrombotic microangiopathy (xTMA), a serious complication related to complement activation and endothelial injury. Treatment with the complement inhibitor eculizumab and plasma exchange successfully resolved the xTMA. Despite this, the patient later experienced repeated episodes of upper gastrointestinal haemorrhage and passed away on day 171.
“This case proves that a genetically engineered pig liver can function in a human for an extended period,” explained lead investigator Beicheng Sun, MD, PhD, Department of Hepatobiliary Surgery, and President of the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. “It is a pivotal step forward, demonstrating both the promise and the remaining hurdles, particularly regarding coagulation dysregulation and immune complications, that must be overcome.”
“This report is a landmark in hepatology,” commented Heiner Wedemeyer, MD, Co-Editor, Journal of Hepatology, and Department. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany, in an accompanying editorial. “It shows that a genetically modified porcine liver can engraft and deliver key hepatic functions in a human recipient. At the same time, it highlights the biological and ethical challenges that remain before such approaches can be translated into wider clinical use. Xenotransplantation may open completely new paths for patients with acute liver failure, acute-on-chronic liver failure, and hepatocellular carcinoma. A new era of transplant hepatology has started.”
“The publication of this case reaffirms the Journal of Hepatology as the world’s leading liver journal. We are committed to presenting cutting-edge translational discoveries that redefine what is possible in hepatology,” added Vlad Ratziu, MD, PhD, Editor in Chief, Journal of Hepatology, and Institute for Cardiometabolism and Nutrition, Sorbonne Université and Hospital Pitié Salpêtrière, Paris, France.
The country that performed the first successful heart transplant has very low organ donation rates. Now a student-run medical non-profit is hoping to make a difference. (Photo: Nasief Manie/Spotlight)
By Elri Voigt
Thousands of people in South Africa are waiting for a life-saving organ transplant, but our very low organ donation rates mean that many won’t get a transplant in time. Spotlight asks the experts why our donation rates are so low and what can be done about it.
Back in 2002, Rentia le Roux received a horrifying diagnosis that her kidneys were failing. “My kids still need me, they are still small, what are we going to do?” Le Roux recalls telling her doctor. After a long journey trying to manage her kidney failure, she would eventually get a kidney from her sister in 2011.
Le Roux, now the chairperson of the Western Cape Transplant Sports Association, is one of the lucky ones. She spoke to Spotlight ahead of a trip to Germany to take part in the 2025 World Transplant Games.
“There are so many people that are on the list waiting for an organ and the waiting period, it can take many years,” she says.
Incomplete data
While there isn’t a coordinated, centralised database of everyone in South Africa who needs a lifesaving organ transplant, various groups do collect data. This is according to Professor David Thomson, an abdominal transplant surgeon and a critical care sub-specialist. Thomson is also the head of the Transplant Centre of Excellence Project at Groote Schuur Hospital in Cape Town.
“Various entities do collect levels of data, but it’s not very centralised and coordinated, and it could be better…we do have the renal registry that’s trying to track the number of people on dialysis, that’s a good source of information,” Thomson says. The Renal registry is a not-for-profit database that collects and publishes data on dialysis and transplant patients in the country. The database itself is an initiative of the South African Nephrology Society, an NPO that aims to further the field of nephrology and improve patient care.
The society estimates that in 2022, just over 9000 people across the public and private healthcare system were receiving “kidney replacement therapy” – which were either medications to help kidney function, dialysis or a kidney transplant.
A report by the South African Transplant society, an NPO that seeks to advance tissue and organ donation and transplantation, estimated that in 2021, across South Africa’s private and public hospitals, 2 586 people were on a waitlist for a lifesaving organ. Of those, 2382 people were waiting for a kidney, 52 needed a liver, 108 needed a heart transplant, and 44 were waiting for a lung.
But in the same year, the report recorded only 229 transplants done across the country.
South Africa does not have a good organ donation culture, says Professor Mignon McCulloch, the head of paediatric nephrology and solid organ transplant at the Red Cross War Memorial Children’s Hospital. In fact, according to McCulloch, and other experts we spoke to, South Africa has some of the lowest transplantation rates in the world.
While we couldn’t find any straightforward ranking system of organ donation rates, reports by the Global Observatory on Donation and Transplantation (GODT) do provide some insight into how some countries compare to one other. In 2017, according to data from the GODT cited in this 2020 study published in the South African Medical Journal, South Africa had 91 deceased donors, which is a rate of 1.6 per million. By contrast, Spain, which is regarded as having one of the highest rates of organ donation in the world, had 2183 deceased donors, a rate of 47.05 per million.
How it works
Organ donation is broadly classified into living donation and deceased donation.
There are two scenarios where someone can become an organ donor. The first, Thomson explains, is when a healthy person donates an organ without which they can live a normal life, like one of their kidneys. The second is when someone has been declared brain dead and is on a mechanical ventilator or when someone has experienced circulatory death -meaning their heart has stopped beating and “futile non-beneficial treatments have been stopped”. The latter is less common in South Africa.
For deceased donation from a brain-dead patient to take place, the potential donor needs to be in an ICU facility on a mechanical ventilator and referred by their clinical team to a transplant coordinator, says Thomson. If that person is eligible, then the transplant team has to get permission from the next of kin who ultimately have the final say even if the potential donor is registered as an organ donor.
“Organ donation can only happen if someone is on a mechanical ventilator in the end-of-life care pathway, so that is always a complicated and emotional discussion,” he says. “Tissue donations such as corneas, bones, skin, that can happen at the mortuary afterwards and there’s a slightly longer period for when these can be successfully recovered but all donation still requires you to have conversations with and get permission from grieving families.”
Juggling resources
McCulloch describes organ donation as being a bit like “a silent Cinderella”, until someone needs a lifesaving transplant, “and then people suddenly start asking questions about why, why don’t we have more transplantation?”
One reason for this is the allocation of resources and competing priorities within the healthcare system.
Thomson says that organ transplants are a “health intensive resource”, and it’s important to acknowledge that it exists in the context of an already overburdened healthcare system. There is a Deputy Director of dialysis and transplantation within the National Department of Health, Thomson explains, but there isn’t an “overarching central coordinating authority supporting deceased donation”. Instead, he says it is driven by hospital groups and within the provincial healthcare departments by healthcare workers
Adding to this, McCulloch says that doctors are always having to “juggle resources” and if there is only one bed available in an ICU, weighing up whether to give it to someone who will potentially become an organ donor or someone with pneumonia and will likely have a good outcome, is difficult.
Another challenge is the limited number of surgeons, physicians, and hospitals with the skill and equipment to perform an organ transplant. This strategy roadmap document by the South African Transplant Society list 21 transplants centres across the whole country – 14 of them offer kidney transplants, six offer heart transplants, four offer lung transplants, four offer liver transplants, and only one offers pancreas transplants.
Graphic of transplant centres in South Africa. (Source: Organ and Tissue Donation in South Africa – Creating a National Strategy Roadmap)
One can save seven
Earlier this year, an unused room in Tygerberg Hospital got a face-lift and a new purpose from a student-run medical non-profit. The initiative called Save7 was kickstarted by a conversation on kidney donation on Stellenbosch University’s Medical Campus. Its initial goal was to raise awareness, particularly among students, that one donor can save up to seven lives. And if tissue like corneas, heart valves, bone and skin are donated, one person can improve the lives of around 50 people.
Jonty Wright, who cofounded Save7, tells Spotlight that the organisation’s founding group of four has now grown to over 200 across multiple universities countrywide. Among others, the group created a Lifepod to solve a transplant-related problem at Tygerberg Hospital. Doctors and staff involved in transplantation at the hospital were citing competing resources as the reason behind low referral rates of potential organ donors by healthcare providers.
The solution posed by Save7, professors on the campus and some of the doctors involved with transplantation was to create a designated bed space for patients who are brain dead and are potential organ donors. The hope was that referrals for potential organ donations would be increased.
The room, Wright says, was an old minor operating theatre and storeroom that belonged to the orthopaedic surgery department and was situated in an ideal spot – in a corridor between the emergency medicine and trauma admissions.
Three of the Save7 co-founders, from left to right Jonty Wright, Suhayl Khalfey and Sachen Naidu. (Photo: Nasief Manie/Spotlight)
About three months ago, after fundraising efforts and backing by the Health Foundation and other partners, the Lifepod opened. The room currently holds a hospital bed, a ventilator on lease from the surgical department, vitals monitor, cardiac monitor, infusion pumps, emergency trolley, fridge, and crash cart. All the things needed to keep someone who is brain dead’s body comfortable and allow the doctors to counsel their loved ones about potentially donating their organs.
So far, according to Wright, referrals of potential candidates for organ donation at Tygerberg have gone up by 500%, but at the time of the interview none of the next of kin have consented to donating their loved one’s organs. (Data on this has not yet been published).
This ties onto another layer of complexity around organ donation, the reasons why next of kin don’t always give permission.
Need for better education
Samantha Nichols, the executive director of operations for the Organ Donor Foundation, an NGO advocating for organ donations, tells Spotlight that the problem isn’t so much a lack of awareness of organ donation, as a lack of good education around it. She says this affects everyone, including healthcare workers.
Nichols says that “it’s almost like the stars have to align” for a deceased donor to donate their organs, because of how many steps and doctors are involved in the process.
“[W]hen a person is sent to an ICU or trauma unit, the team of doctors that work on that person to save their life is a totally different team to the transplant team,” she says. A transplant team is only ever called in if a potential donor has been declared brain dead by two different doctors who aren’t part of or affiliated with a transplant team.
“[O]nly then can they start the process of talking to the family, and then they still need to get consent from the family before the organs are removed,” she says.
The Opt-in versus Opt-out debate
When it comes to consent for organ donation, South Africa has what is referred to as an opt-in system. An opt-in system means that someone must provide explicit consent of their desire to donate an organ. While an opt-out system means all adults are automatically considered organ donors after death, unless they explicitly withdraw consent beforehand.
There has been some debate about whether switching to opt-out systems would improve organ donation rates. One recent study, in which researchers analysed deceased donor rates in five countries that had switched from an opt-in to an opt-out system, did not find an increase in organ donation rates.
“Unless flanked by investments in healthcare, public awareness campaigns, and efforts to address the concerns of the deceased’s relatives, a shift to an opt-out default is unlikely to increase organ donations,” the researchers concluded.
A 2024 editorial in the Lancet medical journal made a similar point, saying “a simplistic switch to the ‘opt-out’ model is alone not sufficient to boost donation”. Instead, it lists the three components that makes Spain’s transplant programme so successful. “A solid legislative framework, strong clinical leadership, and a highly organised logistics network overseen by the National Transplant Organization.” An opt-out system is also unlikely to work well in South Africa from a legislative perspective, since it might be seen by some to impinge upon an “individual’s rights to personal autonomy and bodily and psychological integrity”, as argued in this article in the Conversation.
The experts Spotlight spoke to instead point to several other changes that could be made to improve donation rates.
‘Everyone can do a bit better’
The responsibility around improving organ transplantation rests on us as society and as a coordinated healthcare system, according to Thomson.
“[E]veryone can do a bit better…and I don’t think you want to make it one person’s responsibility for the performance. It’s actually a collective and how we work together,” Thomson says. “…a lot of things like supporting donation actually links into good palliative care services, and that should be something we’re offering to everyone.”
Thomson advocates for upskilling healthcare workers to be able to better counsel families during end-of-life care, not necessarily just around organ donation but around “engaging humanely with “families and end of life and navigating that complexity with them as the healthcare team”.
He recommends making counselling of grieving families and palliative care discussion a hospital system issue, instead of an individual responsibility by adding it to institutional operating standards. “And then you actually need to audit it, measure it, reflect on it and monitor the outcomes,” he says.
Suhayl Khalfey, a Save7 cofounder, says now that the Lifepod is ready to use, their focus is shifting to educate people about the importance of organ donation. As part of its education efforts, Khalfey says Save7 is putting together a database of different religious leaders to help counsel families uncertain about their faith’s stance on organ donation.
Nichols stresses that transplant teams will honour different religious beliefs and funeral practises and that a donor’s body will not appear disfigured in any way after they’ve donated their organs.
Start by having the conversation
Anyone can register as an organ donor with the Organ Donor Foundation, says Nichols. The process is free and will take less than a minute (see their website here). If a situation arises where you are brain dead and you are a candidate for organ donation your family will still need to give permission.
This is why it is so important to have the conversation with your loved ones about what your wishes are, says Khalfey.
Sachen Naidu, another cofounder of Save7, adds to this saying that often with the students they’ve spoken to, organ donation is viewed as something to think about in the distant future. He encourages young people to reconsider this mindset.
Even children can learn about organ donation.
The non-profit organisation Transplant Education for Living Legacies (TELL) recently launched an educational campaign in South Africa aimed at children in the 5 to 11 age group. The initiative, called the Orgamites Mighty Education Programme, is an international child health education programme originating from Canada. At its heart, the programme is a conversation starter, says Thomson who spoke on a TELL webinar.
“All we want is for people to be having educated conversations about it [organ donations],” he says. “Children need transplants too.”
For McCulloch, organ donation goes beyond impacting just the recipients. She uses the example of families who have lost a child in a tragic accident.
“You had a completely well child five minutes ago and then something terrible happened, and now you’ve got a child who’s died and you’re going to go home with a gap in your heart. Whereas at least when you donate [the] organs to another child, something good can come of out of a really hopeless, tragic situation,” she says.
Thomson adds to this saying: “And that’s a memory that lives with that family for a long time afterwards …not just that time point. That’s what they’re going to remember as part of that event, and it really does offer them a degree of solace for a tragedy.”
And the difference to those receiving organs can obviously be life changing. Receiving a kidney gave Le Roux the chance to see her children grow up. “So, every [milestone] when they wrote matric, when they got their degrees, everything. It’s like a step forward, something I can tick off, I’m still here. I’m able, I’m healthy,” she says.
The method, rapid recovery with extended ultra-oxygenated preservation, involves flushing the donor heart with a cold oxygenated preservation solution after death.
Photo by Natanael Melchor on Unsplash
Vanderbilt University Medical Center researchers have developed a groundbreaking new method for the recovery of hearts from deceased organ donors after circulatory death (DCD).
The method, rapid recovery with extended ultra-oxygenated preservation (REUP), involves flushing the donor heart with a cold oxygenated preservation solution after death. This avoids the disadvantages of two existing preservation methods, both of which reanimate the heart, one that has ethical questions and another that is expensive.
The former method known as normothermic regional perfusion (NRP) involves reanimating the heart in the deceased donor’s body, which raises ethical concerns for some and is not allowed in all states or countries. The latter uses ex situ perfusion systems that are costly and laborious, and provide an imperfect and less physiologic reanimation of the heart.
The new method has similar outcomes to existing methods but is simpler and much less expensive, said first author Aaron Williams, MD, in an article just published in the New England Journal of Medicine. He said the technique has great potential to expand the number of donor hearts available by making organ preservation technology more widely available worldwide and expanding the use of DCD hearts.
“It’s something that has never been done in the field of heart transplantation with success,” he said. “I think this is really going to be a game changer. This is going to be a technique that’s going to essentially have worldwide applicability.”
The VUMC team was successful in deploying the method in donor hearts used in three transplants, starting in November 2024. The technique consists of the use of a flush circuit to oxygenate two litres of cold preservation solution that includes packed red cells, del Nido cardioplegia and other additives. To date, VUMC has used the method for 20 transplants, Williams said, with excellent outcomes – similar to, if not better than, the existing techniques.
“This arose out of the problems with the other two methods; the ethical issues with the one and the cost with the other,” Williams said. “We have all been thinking about these issues for some time now. We, as a team, came up with this cardiac preservation solution and technique that helps to resuscitate and protect these DCD hearts well so they can be used for transplantation.”
Williams said the technique has been successful in preserving hearts for more than four hours and to as many as eight.
The use of DCD hearts has changed the transplant field significantly. Over the last five years, Vanderbilt’s heart transplant program has been a leader in utilising hearts from DCD donors, hearts that were previously discarded because they were determined to be too injured and too high risk for subsequent problems. Special preservation techniques that Vanderbilt uses have made it possible to recover DCD hearts and support them for up to 10 hours prior to transplantation. This allows Vanderbilt thoracic organ recovery teams to travel farther in search of organs and add hundreds of organs to the donor pool.
Prior to 2020, Vanderbilt only transplanted organs from DBD (donation after brain death) donors. Like DCD donors, DBD donors have sustained devastating, non-recoverable neurologic injury. Unlike DBD donors, however, DCD donors don’t yet meet formal brain death criteria – as such, the methods that are used for withdrawal of donor life support and surgical retrieval of DCD versus DBD organs differs.
Williams said the new technique described in the paper has only been used on donor hearts, and further study is needed to see if it can be applied to other donor organs, such as livers, kidneys, pancreas and lungs. The technique could also be applied to paediatric transplants. All told, it could increase the pool of available donors and save lives through transplantation.
Current treatments to prevent organ transplant rejection focus mainly on suppressing T cells, part of the adaptive immune system. However, the innate immune system – the body’s first line of defence that triggers early inflammation after transplantation – has largely remained untargeted by modern therapies.
In a new study, researchers from Mass General Brigham identified a natural “brake” within the innate immune system: the inhibitory receptor Siglec-E (SigE) and its human counterparts, Siglec-7 and Siglec-9. This receptor helps prevent overactivation of immune cells that drive rejection. When this brake is missing, inflammation worsens, leading to faster rejection in preclinical models. Importantly, transplant patients with higher levels of Siglec-7 and Siglec-9 showed better graft survival, highlighting this pathway as a promising target for new therapies. Results are published in Science Translational Medicine.
“For decades, we’ve focused almost exclusively on controlling T cells to prevent rejection,” said Leonardo Riella, MD, PhD, medical director of Kidney Transplantation at Massachusetts General Hospital (MGH). Riella is also the Chair in Transplantation at Harvard Medical School. “Our research shows that the innate immune system plays a pivotal role. By harnessing natural inhibitory pathways like Siglec-E, we can develop safer, more precise therapies that protect transplanted organs without compromising overall immune health.”
To conduct their studies, the researchers, led by first author Thiago J. Borges, PhD, of the Center for Transplantation Sciences at MGH, used mouse models of heart, kidney, and skin transplantation to study the roles of SigE, the murine equivalent of Siglec-7 and Siglec-9. Recipients deficient in SigE had accelerated acute rejection and increased inflammation. The researchers also looked at the levels of the receptors in samples from human transplant biopsies, finding that higher levels of the receptors were associated with improved allograft survival, suggesting that the findings in mice will be translatable to organ transplants in humans.
“This discovery paves the way for next-generation treatments that address both arms of the immune system, offering hope for longer-lasting transplant success and reducing the need for lifelong immunosuppression,” said Riella.
The world’s first partial face and whole eye transplant has yielded important insights towards the development of functional eye transplants.
Over one year ago, a surgical team at NYU Langone Health transplanted part of a donor face onto a 46-year old power line worker who had suffered extensive facial injuries and the loss of his left eye. They also transplanted a complete eye into the patient, connecting it up to blood vessels and nerves, to see whether it was possible for an eye to survive. Now, findings on the health of the transplanted eye published in JAMA reveal that the eye is healthy but no light has been seen from it.
For the roughly 40 million people around the world without sight in either eye, stem cell research has been the most recent hope for regaining vision in many cases of trauma and disease.
In the eye transplant, the optic nerve was attached and immunosuppression used. Fluorescein angiography showed that perfusion of the globe and retinal were maintained throughout the immediate postoperative period. Optical coherence tomography revealed atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone.
Crucially, the retina of the transplanted eye responded to light as confirmed by serial electroretinography. MRI scans demonstrated the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye. However, after one year, no light in the eye was observed by the patient.
As discussed in an accompanying editorial published in JAMA Network, whole eye transplantation (WET) has been regarded as one of the most difficult yet important transplant procedures to attempt developing. In 1978, a report from the National Eye Institute advisory stated that “[a]t present, any effort to transplant a mammalian eye is doomed to failure by the ganglion cell axon’s inability to withstand cutting, by the difficulty of insuring adequate circulation of blood to the transplanted eye during or shortly after operation, and lastly by immune rejection of foreign tissue.”
With this transplant case, the issues of adequate circulation and immune rejection have now been shown to be surmountable, the authors point out. Other issues to address concern connecting the cranial nerves to enable opening of the eyelid.
Human colon cancer cells. Credit: National Cancer Institute
Colorectal cancer often metastasises to the liver, and for some patients, surgical removal of their liver tumours is not an option. A new study led by researchers at the Wilmot Cancer Institute and University of Rochester Medical Center (URMC) shows that a select group of patients with colorectal cancer that has spread to the liver tend to fare better if they receive a liver transplant as opposed to other common therapies.
In the study, published in JAMA Surgery, patients who had liver transplants tended to live longer without cancer progression than patients who opted for other treatments. While previous studies have shown the benefits of liver transplants for these patients, this is the first study to compare liver transplants to other treatment options.
“In any cancer treatment, it’s very easy to describe the outcomes of the patients who received the intervention, but similar patients that did not undergo the intervention can serve as a good comparison,” said Matthew Byrne, MD, a surgery resident at URMC and author of the study. “Without randomised, controlled trial data, this study offers the best evidence that is available to understand whether liver transplant provides better outcomes over other treatments.”
The study followed 33 patients whose colorectal cancer was under control, but who had liver tumours that could not be surgically removed. All 33 patients were eligible for liver transplantation, but only 20 chose to have a transplant, while 13 opted for other classical therapies, like removal of part of the liver, chemotherapy, or liver-directed therapies.
Compared to the classical therapy group, the liver transplant group had significantly higher progression-free survival rates across three years of follow-up. One year after liver transplant, 90% of patients showed no signs of cancer progression. That number dropped to 73% after two years and to 36% at three years. On the other hand, only 42% of patients who opted for other therapies were cancer-progression-free after one year, which dropped to roughly 10% after two and three years.
The transplant group also had higher overall survival rates than the standard therapy group, though the difference wasn’t statistically significant. At the three-year follow-up, 90% of transplant patients had survived, compared to 73% of patients who received other therapies.
Though this study provides solid evidence, larger clinical trials will be needed to fully understand the added benefit of liver transplant compared to other treatments for these patients, and to better refine which patients benefit most.
The quest to develop universal donor blood has taken a decisive step forward. Researchers in Denmark have discovered enzymes that, when mixed with red blood cells, are able to remove specific sugars that make up the A and B antigens in the human AB0 blood groups. The results appear in Nature Microbiology.
“For the first time, the new enzyme cocktails not only remove the well-described A and B antigens, but also extended variants previously not recognised as problematic for transfusion safety. We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood. Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production,” says Professor Maher Abou Hachem, who is the study leader at Technical University Denmark (DTU) and one of the senior scientists behind the discovery.
He states that the discovery is the result of combining the expertise of DTU researchers in enzymes from the human gut microbiota and Lund University researchers in carbohydrate-based blood groups and transfusion medicine.
High demand for donor blood
Human red blood cells carry specific complex sugars structures (antigens) that define the four AB0 blood groups A, B, AB and 0. These antigens control compatibility between donors and recipients for safe blood transfusion and organ transplantation. Donor blood is screened for disease markers and the main blood groups. It can then be stored refrigerated for up to 42 days.
The need for donor blood is high due to the elderly making up a larger proportion of the population and more patients undergoing blood-intensive medical procedures. Successfully converting A or B blood types into AB0 universal donor blood can markedly reduce the logistics and costs currently associated with storing four different blood types. In addition, the development of universal donor blood will lead to an increased supply of donor blood by reducing the waste of blood approaching its expiry date.
The reason why it is necessary to remove the A and B antigens to create universal donor blood is because they can trigger life-threatening immune reactions when transfused into non-matched recipients.
The concept of using enzymes to generate universal donor blood was introduced more than 40 years ago. Since then, higher efficiency enzymes to remove the A and B antigens were discovered, but researchers are still not able to explain or abolish all immune reactions related to the blood, and therefore these enzymes are still not used in clinical practice.
Enzymes from the gut
The research groups from DTU and Lund University have gone new ways to find enzymes that can remove both the A and B blood antigens and the sugars that block them. The research teams discovered new mixtures of enzymes from the human gut bacterium Akkermansia muciniphila that feeds by breaking down the mucus, which covers the surface of the gut. It turns out that these enzymes are exceptionally efficient, as the complex sugars at the surface of the intestinal mucosa share chemical resemblance with those found at the surface of blood cells.
“What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group AB0 antigens. This hypothesis turned out to be correct,” says Maher Abou Hachem.
The researchers in this study tested 24 enzymes, which they used to process hundreds of blood samples.
“Universal blood will create a more efficient utilisation of donor blood, and also avoid giving AB0-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient. When we can create AB0-universal donor blood, we will simplify the logistics of transporting and administering safe blood products, while at the same time minimizing blood waste” says Professor Martin L. Olsson, the leader of the study at Lund University.
The researchers from DTU and Lund University have applied for a patent on the new enzymes and the method for enzyme treatment and expect to make further progress on this in their new joint project over the next three and a half years. If successful, the concept needs to be tested in controlled patient trials before this can be considered for commercial production and clinical use.
The initial research project is funded by the Independent Research Fund Denmark (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and county councils as well as the Knut and Alice Wallenberg Foundation and Research Fund Denmark, Natural Sciences, FNU), while the new continued project is funded by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.
The AB0 blood group antigens found on the surface of red blood cells are also found on the mucosal layer that lines the surface of the gut. Researchers have harnessed a specialised human gut bacterium and its ability to use these antigens as nutrients to discover and develop two enzyme mixtures that convert group A and B red blood cells into universal donor blood. Graphic: Mathias Jensen, postdoc at DTU.
About Akkermansia muciniphila
Akkermansia muciniphila is a bacterium found abundantly in the guts of most healthy humans. This bacterium can break down mucus in the gut and produces beneficial compounds such as the short-chain fatty acid propionate, in addition to exerting beneficial effects on body weight and metabolic markers.
Familial Alzheimer’s disease can be transferred via bone marrow transplant, researchers show in the journal Stem Cell Reports. When the team transplanted bone marrow stem cells from mice carrying a hereditary version of Alzheimer’s disease into normal lab mice, the recipients developed Alzheimer’s disease – and at an accelerated rate.
The study highlights the role of amyloid that originates outside of the brain in the development of Alzheimer’s disease, which changes the paradigm of Alzheimer’s from being a disease that is exclusively produced in the brain to a more systemic disease. Based on their findings, the researchers say that donors of blood, tissue, organ, and stem cells should be screened for Alzheimer’s disease to prevent its inadvertent transfer during blood product transfusions and cellular therapies.
“This supports the idea that Alzheimer’s is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathology,” says senior author and immunologist Wilfred Jefferies, of the University of British Columbia. “As we continue to explore this mechanism, Alzheimer’s disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human derived stem cells or blood products.”
To test whether a peripheral source of amyloid could contribute to the development of Alzheimer’s in the brain, the researchers transplanted bone marrow containing stem cells from mice carrying a familial version of the disease — a variant of the human amyloid precursor protein (APP) gene, which, when cleaved, misfolded and aggregated, forms the amyloid plaques that are a hallmark of Alzheimer’s disease. They performed transplants into two different strains of recipient mice: APP-knockout mice that lacked an APP gene altogether, and mice that carried a normal APP gene.
In this model of heritable Alzheimer’s disease, mice usually begin developing plaques at 9 to 10 months of age, and behavioural signs of cognitive decline begin to appear at 11 to 12 months of age. Surprisingly, the transplant recipients began showing symptoms of cognitive decline much earlier – at 6 months post-transplant for the APP-knockout mice and at 9 months for the “normal” mice.
“The fact that we could see significant behavioural differences and cognitive decline in the APP-knockouts at 6 months was surprising but also intriguing because it just showed the appearance of the disease that was being accelerated after being transferred,” says first author Chaahat Singh of the University of British Columbia.
In mice, signs of cognitive decline present as an absence of normal fear and a loss of short and long-term memory. Both groups of recipient mice also showed clear molecular and cellular hallmarks of Alzheimer’s disease, including leaky blood-brain barriers and buildup of amyloid in the brain.
Observing the transfer of disease in APP-knockout mice that lacked an APP gene altogether, the team concluded that the mutated gene in the donor cells can cause the disease and observing that recipient animals that carried a normal APP gene are susceptible to the disease suggests that the disease can be transferred to health individuals.
Because the transplanted stem cells were hematopoietic cells, meaning that they could develop into blood and immune cells but not neurons, the researchers’ demonstration of amyloid in the brains of APP knockout mice shows definitively that Alzheimer’s disease can result from amyloid that is produced outside of the central nervous system.
Finally the source of the disease in mice is a human APP gene demonstrating the mutated human gene can transfer the disease in a different species.
In future studies, the researchers plan to test whether transplanting tissues from normal mice to mice with familial Alzheimer’s could mitigate the disease and to test whether the disease is also transferable via other types of transplants or transfusions and to expand the investigation of the transfer of disease between species.
“In this study, we examined bone marrow and stem cells transplantation. However, next it will be important to examine if inadvertent transmission of disease takes place during the application of other forms of cellular therapies, as well as to directly examine the transfer of disease from contaminated sources, independent from cellular mechanisms,” says Jefferies.
Surgeons prepare the pig kidney for transplantation. Credit: Massachusetts General Hospital
Massachusetts General Hospital (MGH) has announced the world’s first successful transplant of a genetically-edited pig porcine) kidney into a 62-year-old man living with end-stage kidney disease (ESKD). Surgeons from the Mass General Transplant Center conducted the four-hour-long surgery on Saturday, March 16. The procedure marks a major milestone in the quest to provide more readily available organs to patients. Mass General Brigham is an internationally recognised leader in transplantation services, providing advanced care for a wide spectrum of organ and tissue transplants throughout its renowned academic medical system.
Under the leadership of Leonardo V. Riella, MD, PhD, Medical Director for Kidney Transplantation, Tatsuo Kawai, MD, PhD, Director of the Legorreta Center for Clinical Transplant Tolerance, along with Nahel Elias, MD, Interim Chief of Transplant Surgery and Surgical Director for Kidney Transplantation, a genetically-edited pig kidney with 69 genomic edits was successfully transplanted into a living patient.
Mass General Brigham has a rich history in organ transplant innovation, including the world’s first successful human organ transplant (kidney) performed at Brigham and Women’s Hospital in 1954 and the nation’s first penile transplant, performed at MGH in 2016. Mass General Brigham transplantation programs draw upon the deep, integrated expertise of some of the world’s leading transplant physicians and scientists who collaborate across experienced multidisciplinary teams to advance medicine and improve the lives of patients.
“Mass General Brigham researchers and clinicians are constantly pushing the boundaries of science to transform medicine and solve significant health issues facing our patients in their daily lives,” said Anne Klibanski, MD, President and CEO, Mass General Brigham. “Nearly seven decades after the first successful kidney transplant, our clinicians have once again demonstrated our commitment to provide innovative treatments and help ease the burden of disease for our patients and others around the world.”
“The tireless commitment of our clinicians, researchers and scientists to improving the lives of our transplant patients – both current and future – is at the very heart and soul of academic medicine and what it means to work and provide care at Mass General Brigham,” said David F. M. Brown, MD, President, Academic Medical Centers, Mass General Brigham. “We are so thankful to the incredible staff throughout our hospitals who helped make this surgery a success, and to the patient for his bravery and courage.”
“The success of this transplant is the culmination of efforts by thousands of scientists and physicians over several decades. We are privileged to have played a significant role in this milestone. Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure,” Kawai said.
The pig kidney was provided by eGenesis, from a pig donor that was genetically-edited using CRISPR-Cas9 technology to remove harmful pig genes and add certain human genes to improve its compatibility with humans. Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of infection in humans. Over the past five years, MGH and eGenesis have conducted extensive collaborative research, with the findings published in Nature in 2023.
This successful procedure in a living recipient is a historic milestone in the emerging field of xenotransplantation – the transplantation of organs or tissues from one species to another – as a potential solution to the worldwide organ shortage. According to the United Network for Organ Sharing (UNOS), more than 100 000 people in the U.S. await an organ for transplant and 17 people die each day waiting for an organ. A kidney is the most common organ needed for transplant, and end-stage kidney disease rates are estimated to increase 29-68% in the U.S. by 2030, according to literature published in the Journal of the American Society of Nephrology.
The patient, Mr. Richard ‘Rick’ Slayman of Weymouth, Mass., is recovering well at MGH and is expected to be discharged soon.
“The real hero today is the patient, Mr Slayman, as the success of this pioneering surgery, once deemed unimaginable, would not have been possible without his courage and willingness to embark on a journey into uncharted medical territory. As the global medical community celebrates this monumental achievement, Mr Slayman becomes a beacon of hope for countless individuals suffering from end-stage renal disease and opens a new frontier in organ transplantation,” said Joren C. Madsen, MD, DPhil, Director of the MGH Transplant Center.
Mr Slayman said in a statement, “I have been a Mass General Transplant Center patient for 11 years and have the highest level of trust in the doctors, nurses, and clinical staff who have cared for me. When my transplanted kidney began failing in 2023, I again trusted my care team at MGH to meet my goals of not just improving my quality of life but extending it. My nephrologist, Dr Winfred Williams, MD and the Transplant Center team suggested a pig kidney transplant, carefully explaining the pros and cons of this procedure. I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive. I want to thank everyone at MGH who has cared for me, especially Dr Williams, Dr Kawai, the surgeon who performed my first kidney transplant and now this one, and Dr Riella, who has orchestrated the logistics behind this new transplant. They have supported me during every step of the journey, and I have faith they will continue to do so.”
Mr Slayman, who has been living with Type 2 diabetes and hypertension for many years, previously received a kidney transplant from a human deceased donor in December 2018, performed at MGH by Kawai, after being on dialysis seven years prior. The transplanted kidney showed signs of failure approximately five years later and Mr Slayman resumed dialysis in May 2023. Since resuming dialysis, he encountered recurrent dialysis vascular access complications requiring visits to the hospital every two weeks for de-clotting and surgical revisions, significantly impacting his quality of life and a common problem among dialysis patients.
“The continued success of this groundbreaking kidney transplant represents a true milestone in the field of transplantation. It also represents a potential breakthrough in solving one of the more intractable problems in our field, that being unequal access for ethnic minority patients to the opportunity for kidney transplants due to the extreme donor organ shortage and other system-based barriers. This health disparity has been the target of many national policy initiatives for over 30 years, with only limited success. An abundant supply of organs resulting from this technological advance may go far to finally achieve health equity and offer the best solution to kidney failure – a well-functioning kidney – to all patients in need. I commend Mr Slayman, who has been my patient for many years, for his courageousness in becoming a trailblazer in the field of transplantation,” Williams said.
The procedure was performed under a single FDA Expanded Access Protocol (EAP) – known as compassionate use – granted to a single patient or group of patients with serious, life-threatening illnesses or conditions to gain access to experimental treatments or trials when no comparable treatment options or therapies exist. Mr. Slayman also received infusion of novel immunosuppressant drugs, tegoprubart, provided by Eledon Pharmaceuticals, Inc., and ravulizumab, provided by Alexion Pharmaceuticals, Inc.
