Lab-Grown Mini Kidneys Are Bringing Science Closer to Custom Organs
Science's dream of creating perfect custom organs on demand as soon as a patient needs one is still a long way off. But tiny versions are already serving as useful research tools and stepping stones toward full-fledged replacements.
Although organoids cannot yet replace kidneys, they are invaluable tools for research.
Australian researchers have grown hundreds of mini human kidneys in the past few years. Known as organoids, they function much like their full-grown counterparts, minus a few features due to a lack of blood supply.
Cultivated in a petri dish, these kidneys are still a shadow of their human counterparts. They grow no larger than one-sixth of an inch in diameter; fully developed organs are up to five inches in length. They contain no more than a few dozen nephrons, the kidney's individual blood-filtering unit, whereas a fully-grown kidney has about 1 million nephrons. And the dish variety live for just a few weeks.
An organoid kidney created by the Murdoch Children's Institute in Melbourne, Australia.
Photo Credit: Shahnaz Khan.
But Melissa Little, head of the kidney research laboratory at the Murdoch Children's Institute in Melbourne, says these organoids are invaluable tools for research. Although renal failure is rare in children, more than half of those who suffer from such a disorder inherited it.
The mini kidneys enable scientists to better understand the progression of such disorders because they can be grown with a patient's specific genetic condition.
Mature stem cells can be extracted from a patient's blood sample and then reprogrammed to become like embryonic cells, able to turn into any type of cell in the body. It's akin to walking back the clock so that the cells regain unlimited potential for development. (The Japanese scientist who pioneered this technique was awarded the Nobel Prize in 2012.) These "induced pluripotent stem cells" can then be chemically coaxed to grow into mini kidneys that have the patient's genetic disorder.
"The (genetic) defects are quite clear in the organoids, and they can be monitored in the dish," Little says. To date, her research team has created organoids from 20 different stem cell lines.
Medication regimens can also be tested on the organoids, allowing specific tailoring for each patient. For now, such testing remains restricted to mice, but Little says it eventually will be done on human organoids so that the results can more accurately reflect how a given patient will respond to particular drugs.
Although these organoids cannot yet replace kidneys, Little says they may plug a huge gap in renal care by assisting in developing new treatments for chronic conditions. Currently, most patients with a serious kidney disorder see their options narrow to dialysis or organ transplantation. The former not only requires multiple sessions a week, but takes a huge toll on patient health.
Ten percent of older patients on dialysis die every year in the U.S. Aside from the physical trauma of organ transplantation, finding a suitable donor outside of a family member can be difficult.
"This is just another great example of the potential of pluripotent stem cells."
Meanwhile, the ongoing creation of organoids is supplying Little and her colleagues with enough information to create larger and more functional organs in the future. According to Little, researchers in the Netherlands, for example, have found that implanting organoids in mice leads to the creation of vascular growth, a potential pathway toward creating bigger and better kidneys.
And while Little acknowledges that creating a fully-formed custom organ is the ultimate goal, the mini organs are an important bridge step.
"This is just another great example of the potential of pluripotent stem cells, and I am just passionate to see it do some good."
In 1962, the world was a remarkably different place: Neil Armstrong had yet to take his first steps on the lunar surface, John F. Kennedy was serving as president of the United States, and the Beatles were still a few years away from superstardom, having just recorded their first single.
The word “measles” was also a household name. Measles, which still exists in parts of the world today, is a highly contagious viral infection that typically causes fever, cough, muscle pain, fatigue, and a distinctive red rash. Measles was so pervasive around the world in 1962 that most children had gotten sick with it before the age of fifteen—but even though it was common, it was far from harmless. Measles killed around 400 to 500 people per year in the United States, and approximately 2.6 million people each year worldwide. Countless others suffered severe complications from measles, such as permanent blindness.
Tragedy hits home
Author Roald Dahl at his Buckinghamshire home with Olivia, daughter Chantal, and wife Patricia Neal in 1960.
Ben Martin / Getty Images
That year, British author Roald Dahl was beginning to make a name for himself, having just published his best-selling book James and the Giant Peach. Dahl, who would go on to write some of the most well-loved children’s books of the century, lived in southern England with his wife and three children. One day, Dahl and his wife, actress Patricia Neal, received word that there was an outbreak of measles at his daughters’ school.
While some parents quarantined their children, many others also considered measles a harmless childhood disease. Neal later recalled in her autobiography that a family member had advised her to “let the girls get measles,” thinking it would strengthen their immune systems and be “good for them.” Reluctantly, Dahl and Neal let their two school-aged children, Olivia and Chantal, continue school. Olivia, then aged seven, fell sick with the measles not long after that.
Neither Dahl nor Neal were terribly concerned about Olivia’s infection. Dahl would write later that it seemed to be taking its “usual course,” and the two would read and spend time together while Olivia rested. After a few days of fever and fatigue, Dahl wrote, Olivia seemed like she was “well on the road to recovery.”
But one afternoon, as the two sat on Olivia’s bed making animals out of pipe cleaners, Dahl noticed that Olivia’s “fingers and her mind were not working together.” When Dahl asked how she was feeling, Olivia replied, “I feel all sleepy.”
Within an hour, Dahl wrote, Olivia was unconscious. Within 12 hours, she was dead.
Olivia died of measles encephalitis, an inflammation of the brain caused by an infection. Approximately 1 in 1,000 people infected with measles develop encephalitis, and of those who develop it, between 10 and 20 percent will die.
Dahl was overcome with grief and wracked with guilt for being unable to prevent his daughter’s death. Mourning, Dahl threw himself into his writing and, in his spare time, spent hours lovingly constructing a rock garden on Olivia’s grave in a local churchyard.
After Olivia’s death, Dahl wrote sixteen novels and several collections of short stories, including Matilda, Fantastic Mr. Fox, and Willy Wonka and the Chocolate Factory, which garnered him worldwide acclaim. His most influential piece of writing, however, wasn’t written until 1986.
A father's plea
Roald Dahl and the open letter he wrote in 1986, encouraging parents to vaccinate their children against measles.
By 1986, measles was no longer the global health threat that it had been in the 1960s, thanks to a measles vaccine that became available just one year after Olivia had died. Still, in the United Kingdom alone, approximately 80,000 people every year were infected with measles. This bothered Dahl, especially since measles rates in the United States had dropped by 98 percent compared to pre-vaccine years. “Why do we have so much measles in Britain when the Americans have virtually gotten rid of it?,” Dahl was reported to have said.
So Dahl set out to prevent a tragedy like Olivia’s from happening again. With encouragement from several prominent public health activists, Dahl wrote an open letter addressed to parents in the UK. The letter recounted his daughter’s death from encephalitis and begged parents to protect their own children from measles:
“...there is today something that parents can do to make sure that this sort of tragedy does not happen to a child of theirs. They can insist that their child is immunised [sic] against measles. I was unable to do that for Olivia in 1962 because in those days a reliable measles vaccine had not been discovered. Today a good and safe vaccine is available to every family and all you have to do is to ask your doctor to administer it.”
Dahl went on to say that although many parents still viewed measles as a harmless illness, he knew from experience that it was not. Measles was capable of causing disability and death, Dahl wrote, whereas a child had a better chance of “choking on a chocolate bar” than developing any serious complication from the vaccine. Dahl ended his letter by saying how happy he knew Olivia would be “if only she could know that her death had helped to save a good deal of illness and death among other children.”
Dahl’s letter was published in early 1986 and distributed to local healthcare workers, schools, and to parents of children who were particularly at risk. As the letter circulated, vaccination rates continued to climb year after year.
Thirty-one years after Dahl’s letter was published, and 55 years after Olivia’s death, the World Health Organization declared in 2017 that measles had officially been eradicated for the first time in the UK thanks to high rates of vaccination.
A small step back
As vaccination rates decline, measles is now making a strong comeback in the United States and elsewhere.
Today, vaccination rates for the measles are in decline, and countries like the UK and the US, who had once eradicated measles completely, are now seeing a comeback. The Centers for Disease Control and Prevention (CDC) recently reported that between December 1, 2023 and January 23, 2024, 23 cases of measles had been confirmed across multiple states. The majority of these cases, they reported, were among children and adolescents who had traveled internationally and had not yet been vaccinated even though they were eligible to do so.
Roald Dahl passed away in 1990, but fortunately, his writing continues to live on. While readers can explore fantastical worlds through his novels and short stories, they can also look back to a reality when tragic deaths like Olivia’s happened far too often. The difference is that today, thanks to modern science, we now have the tools to stop them.
Sarah Watts is a health and science writer based in Chicago.
On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013.He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business