From Myths to Molecules: Stem cells, CAR-Ts, and an Electric Nose

The Fountain of Youth is probably one of the oldest and most popular myths in human culture, and who hasn’t at least once dreamed of it? The fountain itself may be a myth, but thanks to research in stem cells and other emerging technologies, some forms of rejuvenation may not be all that far away. At LINO23, we got a chance to witness how the pioneering work of Nobel Laureates is continued by young researchers, and how all this work hints at a tantalizing new future where we can improve our longevity and wellbeing.

Collaboration is the Way

„Embryonic stem cells have had and are having a considerable impact on understanding the development, cell differentiation, and genetic function. They have also opened prospects of cellular terapies,“ said Sir Martin Evans in his lecture. Evans, along with Matthew Kaufman, was the first to culture mice embryonic stem cells and cultivate them in a lab. For this work, he (along with Oliver Smithies and Mario Capecchi) was awarded the 2007 Nobel Prize in Physiology or Medicine.

It’s hard to overstate just how impactful Sir Martin’s work has been. Embryonic stem cells can be adapted for a wide variety of medical purposes and fundamental biological research, and his discoveries are now being applied in virtually all fields of bioscience. The laureate took the stage to share his journey in research — but he spent just as much time talking about other people’s work.

It is often said that no one accomplishes anything alone, and Sir Martin’s presentation was a brilliant illustration of that. Modern science isn’t about people working by themselves in an ivory tower, it’s about collaboration, reaching out to other people and having other people reach out to you. „Don’t be scared of people out there,“ the laureate encouraged the audience.

Of course, the journey towards groundbreaking research is rarely (if ever) straightforward. Evans discussed the relationship between stem cells in culture, their ability to form tumors in mice, and their origin from embryos, mentioning the many challenges and adventures in his attempts to culture stem cells and induce their differentiation. Most of the time, these challenges were scientific. But sometimes, they were rather unpredictable, like carrying a big black box in the London tube at a time when terrorist attacks ran rife.

„Anything more like a cartoon bomb, you cannot imagine! But I was traveling back and forth and no one ever questioned me,“ Sir Martin recalls.

Evans and Kaufman cultivated embryonic stem cells in cell cultures, genetically altered the stem cells, and implanted them into the uteruses of female mice, growing offspring. Ultimately, Evans and his collaborators demonstrated that they could insert a novel gene into embryonic stem cells that were being cultured. They then utilized these genetically modified cells to create chimeric embryos.

Sir Martin also discussed the importance of keeping this technology in the public domain, something which would go on to greatly accelerate research in the field of stem cells.

„I published this as an abstract as soon as possible because we were afraid that someone would get this patented. We didn’t want this patented! We wanted it in the public domain.“

Continuing Pioneering Science

Sir Martin’s work was continued and advanced by numerous scientists, including some of the young researchers preset at LINO23.

For instance, at a Next Gen session on genetics, biochemistry, and cell biology, Sergiy Velychko presented a way to induce naive pluripotency across different species.

In fact, the two had a meaningful exchange following Velychko’s presentation, with the laureate asking the question and the young researcher responding – a prime example of scientific communication.

In addition to rejuvenation, another aspect that is of utmost importance is our relentless fight against disease. This is where medical research meets the frontlines of healthcare, merging cutting-edge biotechnology with clinical meaningfulness. At the Emerging Technologies / Cancer Next Gen session, young researchers presented a broad sample of how this cutting edge research is promising to improve human health.

Adrian Gottschlich, from the University Hospital of the LMU Munich, Germany discussed how CAR-T cell therapy can be used for treating acute myeloid leukemia, the most common type of leukemia in adults.

„The use of immunotherapies has been continuously increasing over the last years. Of these immunotherapeutic agents, there are different kinds, and especially cellular and T-cell engaging therapies are continuously rising.“

CAR-T cells (Chimeric Antigen Receptor T cells) are a type of immune cell that has been engineered in the laboratory to produce a specific protein on their surface. These cells have been used against some types of cancer, but acute myeloid leukemia (AML) cannot currently be treated with CAR-T cell immunotherapy. This is where Gottschlich’s work comes in. He and his colleagues used bioinformatic analyses to find two candidates out of 25,000 potential cell surface molecules. The resulting cells not only destroy tumors, but also hardly affect the healthy tissue around them. Now, the researcher is working on developing cells to be used for clinical trials.

Meanwhile, Joel Rurik from Karolinska Institutet, Sweden, used CAR-T cells for something very different: treating cardiac disease.

While they can be good against cancer, CAR-T cells pose a problem for dealing with heart problems: the fibroblast response is critical, especially in regards to acute injury (which is often a major concern). So Rurik wanted to see whether he can get RNA to get the CAR-T instructions against fibroblasts. Essentially, he and his colleagues created CAR-T cells in vivo using mRNA. In animal models, these cells were found to improve cardiac function after injury.

„With a single vaccine-like therapeutic RNA, we get a recovery of the function and corresponding fibrosis readouts. I think this is a really incredible result,“ Rurik mentioned.

Clinical advancements come in multiple forms, and indeed, Antonia Morita I. Saktiawati, from Universitas Gadjah Mada in Indonesia, presented a very different project. Saktiawati works on an „electric nose,“ an equipment that can diagnose various conditions or infections using olfactory inputs, to diagnose tuberculosis. Bringing a toothbrush and a deodorant on stage to illustrate her point, the young researcher explained that body odor can be a sign of disease.

„You only need to breathe in the air-collecting back,“ Saktiawati explains. „It works similar to our nose. The chemical sensors in the e-nose will catch the airborne molecules from a sample and will then change it into signal that will recognized by a pattern recognition done by AI. This is similar to what happens in our brain.“

With this approach, the researcher and her colleagues obtained high specificity and sensitivity, and the advantage of the method is that it doesn’t only work for tuberculosis — it can be deployed for myriad diseases. Saktiawati ended with a quote from Louis Pasteur, saying that if we don’t diagnose and treat conditions effectively, it is the microbes who will have the last word.

But looking at the wide array of solutions in development or already developed, you get the feel that perhaps, we humans also have a chance of having the last word. While we have yet to find the mythical fountain of youth, we’re already on a path where modern science can profoundly improve our ability to stay healthier for longer.

However, the future won’t just be about new technological advancements. It will also be about ensuring these advancements are accessible and beneficial for all. Sir Martin’s commitment to keeping his embryonic stem cell technology in the public domain served as a potent reminder of the importance of public access to scientific advancements. Perhaps, in this altruism lies something even more valuable than the Fountain of Youth.