Asuka Koda, Contributing Photographer

At Yale, researchers are using stem cells to grow brain organoids for psychiatric research, regenerate tissues for cancer patients and reprogram blood to reverse immune aging. Despite political headwinds through administrations from Bush to Trump, the Yale Stem Cell Center has emerged as a global leader in regenerative medicine.

“As we live longer, a lot of previously ‘not noticeable’ diseases have become obvious — for

example, neurodegenerative diseases, organ failure, tissue failure, and even cancer, which

actually is an aging disease,” Haifan Lin, the founding director of the Yale Stem Cell Center, said. “To address all these pressing clinical needs, we really need to work on stem cells, because they are the mother cells of all cells in our bodies.”

When scientists first isolated human embryonic stem cells in 1998, they unlocked unprecedented potential to regenerate damaged tissues. However, because the process required destroying surplus IVF embryos, it sparked intense political and moral controversy in the U.S.

In 2001, President George W. Bush restricted federal funding to pre-existing stem cell lines, many of which were unstable or unusable. The policy stalled U.S. research, while countries with more permissive regulations advanced. In response, states like Connecticut launched their own funding efforts — a key reason why Lin left Duke to launch the Yale Stem Cell Center.

Political interference at Yale

Lin credits his decision to join Yale to the uniquely collaborative environment at the School of Medicine.

“There’s no barrier between the clinical and basic research side,” he said, describing a level of integration he found rare in academia.

Even with the intellectual flexibility offered at Yale and the independent funding of stem cell research from Connecticut, Lin still faced barriers after the Bush administration. 

Despite Connecticut’s independent funding for stem cell research, Lin encountered political challenges. During the first Trump administration, he was investigated under the Department of Justice’s China Initiative, a controversial program aimed at prosecuting alleged Chinese espionage in American research and industry. 

In January 2022, Lin was temporarily suspended from Yale and barred from running his lab. The government never made clear the basis of its allegations, and in April of the same year, the case was dropped by the Biden administration. Yale subsequently lifted Lin’s suspension.

The potential of stem cells

Every human begins as a single cell which contains all the genetic information needed to develop into every type of cell in the human body. Its ability to give rise to all other cell types is called potency, a term used in biology to describe a stem cell’s developmental potential. 

When asked if this means that scientists can grow humans in petri dishes, Lin said, “Theoretically, it’s possible, but ethically, that’s not right. But it has been achieved in animals. You can completely build a new mouse using iPSCs.”

What Lin was referring to was induced pluripotent stem cells, or iPSCs, reprogrammed adult cells that turn them back into an embryonic-like state without using embryos. iPSCs have largely replaced embryonic stem cell lines in research. 

Lin compares this to reversing time. He explains, if someone is 60 years old and they seek to artificially induce their own cells into iPSCs, they now have their own cells that are 60 years younger that can do everything embryonic stem cells can do without issues of immune rejection. 

Lin proposed five ways he sees stem cells transforming the medical landscape: tissue and organ repair, anti-aging, cancer treatments, addressing infertility and being tools for pharmaceutical research. Instead of traditionally using animal organs for experimentation, scientists have the technology to build organoids using stem cells that would offer more accurate and human-relevant results than traditional animal models.

With stem cells, Lin explains how scientists are already starting to create individualized treatments for patients, their specific physiology and internal microenvironments. Similar to eastern medicine, especially Chinese medicine, Lin explains, where treatment regimens are personalized to the person’s physiology, scientists have already started to develop drugs and cancer treatment plans tailored to individuals. 

Brain in a dish: the road to curing autism and bipolar disorder

At the Stem Cell Center, In-Hyun Park is using stem cells to reconstruct the human brain in miniature. His lab studies brain organoids, three-dimensional brain-like structures grown from stem cells that mimic early human brain development.

“We use human brain organoids, 3D structures you can generate from stem cells,” Park said. “Using brain organoids, people can model human brain disorders, including neuropsychiatric disorders, neurodevelopmental, as well as neurodegenerative disorders.”

In his lab, the focus is on modeling autism spectrum disorder and bipolar disorder by building advanced organoid systems using stem cells that represent different regions of the brain. 

These models could help identify personalized treatments. He envisions a future in which a patient’s own organoids can be used to test treatments in the lab, instead of experimenting on the patient’s brain. By working with brain organoids, researchers can observe how neurological diseases might emerge long before birth. 

Park’s research seeks to map how different mutations shape brain development at the molecular level. 

“We will have a little bit of a better idea of how different [genetic] mutations cause distinct and common phenotypes related to Autism Spectrum Disorder.”

Park’s bipolar research also explores an entirely different biological question: energy. His lab is investigating the role of mitochondria, the cell’s energy producers, in the manic and depressive phases of bipolar disorder.

That research, he explained, could open new treatment avenues for patients who don’t respond to traditional mood stabilizers like lithium. 

More broadly, Park sees brain organoids as a way to overcome the limitations of decades of neuroscience research built on animal models. He explains that we actually know less about the human brain than we think. 

In the long term, Park envisions two possibilities: using brain organoids as platforms for drug discovery and, eventually, transplantation therapies. He mentions the possibility of making a part of the brain and transplanting it into the “malfunctioning” brain of patients. 

Growing parathyroids: a new hope for post-surgical cancer patients 

Also at the Stem Cell Center, Diane Krause is working on a different frontier of regenerative medicine: growing and transplanting parathyroid glands, which are often damaged or removed during thyroid cancer surgery.

The parathyroid glands, four rice-sized structures tucked behind the thyroid, play a critical role in regulating calcium levels in the body. Just as the pancreas secretes insulin to control glucose, the parathyroid glands secrete parathyroid hormone to maintain calcium homeostasis. When these glands are removed or damaged during surgery, patients can develop hypoparathyroidism, a condition that causes dangerously low calcium levels.

While early symptoms include tingling in the lips and muscle cramps, severe cases can escalate to tetany — a state where muscles seize up entirely, making it difficult to breathe. According to Krause, patients live in constant fear of calcium crashes, often overshooting treatment with supplements and risking kidney stones and long-term organ damage. Unlike insulin, which can be regulated through wearable pumps, calcium lacks comparable technology that allows patients to easily manage their levels independently.

Current treatments offer no long-term cure and often fail to mimic the body’s natural regulation of calcium. 

Inspired by the success of beta cell transplants for diabetes, Krause’s team is working on making parathyroid cells from a patient’s own stem cells. They start with induced pluripotent stem cells and guide them through early developmental stages — like those that happen in embryos — to try and form parathyroid cells. But the parathyroid is a difficult organ to recreate.

“We’re really close,” Krause said. Her team uses genetically modified mice that glow green when parathyroid genes are activated. 

Krause envisions a future where stem-cell-derived parathyroids could be transplanted into patients — possibly even as an off-the-shelf therapy. 

Reprogramming blood: Fighting immune aging 

As humans age, their bodies change on a cellular level that shapes how their immune systems respond to disease. Shangqin Guo studies how aging rewires the behavior of hematopoietic stem cells — the adult stem cells in our bone marrow that continuously generate new blood and immune cells.

When young, the body’s bone marrow produces a balanced mix of immune cells, including both myeloid cells — the first responders like macrophages and neutrophils that use aggressive responses — and lymphoid cells, like B cells and T cells, which provide long-term, targeted immunity. But as Guo explained, that balance shifts with age.

“These cells become exaggerated at making the myeloid cells,” she explained. “But they are getting poorer and poorer for making lymphoid cells. Older people still make immune cells, but they make the wrong kind of immune cells or make them in wrong quantities,” she said. 

That shift means aging bodies produce plenty of inflammatory cells — which flood a site of injury or infection and trigger an immune response — but too few of the immune cells needed to precisely eliminate threats.

The result is constant chronic inflammation in the body, which is linked to a wide range of age-related diseases.  

Now, her lab is searching for those human enzymes that may be quietly dismantling our immune resilience. If they can be identified and inhibited, it might be possible to restore the stem cell’s original programming and reboot the immune system’s balance, not just stalling aging, but reversing its cellular signature. Meanwhile, they are testing whether HIV protease inhibitors, drugs originally designed to stop viruses from replicating, may also help preserve this histone in human cells.

Directing Immunity: The tangents of stem cell science

While many researchers at the Center work directly on manipulating stem cells, Jun Lu’s research explores a different angle, one with wide implications for how stem cell-derived therapies might function in the body.

Lu’s lab discovered that a certain class of “sugar-coated” RNAs appears on the surface of immune cells, not just inside them — a breakthrough with implications for how researchers might one day guide cell-based therapies to the right tissues. 

“If we get rid of these RNAs, they cannot go to certain places in the body,” he said. “So using this way, we basically can have a potential way to control where immune cells go.”

While his team isn’t directly working on stem cells, the delivery, targeting and fate of immune cells are questions that mirror challenges in regenerative medicine. 

Lu’s research is not just about growing or reprogramming cells, but understanding how to guide them once they’re inside the body. 

The rulebook of development

Andrew Xiao doesn’t work with stem cells in the traditional sense. 

“I was hired by Yale and the Stem Cell Center not because I have stem cell specialties,” he said, “it’s because I know how DNA interprets their own information.” 

His research focuses on epigenetics — the molecular “rulebook” that determines how the same DNA can give rise to radically different cell types. 

Instead of using different DNA, the body uses the same genetic text and reads it differently, like highlighting different sentences in the same book.

Xiao’s lab investigates the phase of development before the embryo implants into the uterus, when the usual biological “rules” don’t seem to apply. 

“The rules are kind of like a wild, wild West … there’s no rules,” he said. “But somehow, miraculously, the human baby becomes a human. The human baby didn’t become a chimpanzee.”

Much of his work focuses on trophoblast cells, which form the placenta — a structure essential to pregnancy that’s often overlooked in stem cell research. These cells have a set of rules that are almost exclusively used once in very early embryos and never utilized again.

Understanding how these rules work, Xiao says, is not just about placentas; it has implications in cancer research and treatment.  

Xiao’s team found that iPSCs sometimes adopt placental traits too strongly. Sometimes, the iPSCs become the placenta instead of embryos. Blocking that is a part of the challenge. 

By uncovering these hidden developmental pathways, Xiao hopes to improve both stem cell therapies and cancer treatments. 

The future of stem cells

According to Dale Kutnick ’72, advisor to the Yale Stem Cell Center, political interference is only one of the obstacles facing the field. He believes misinformation is a deeper and more persistent threat.

He writes, “The lack of understanding among most (90%+) people about the true implications on the evolution of Homo Sapiens during the next 50+ years will cause some funding issues as well as regulatory attempts.” 

He argues that this is ultimately self-sabotaging, as he believes that stem cell research will change humans’ evolutionary trajectory. 

He starts by saying that genetic engineering of stem cells will eliminate genetically transmitted diseases and other afflictions, like diabetes and cystic fibrosis, before they manifest. Stem cell treatments can also address environmentally induced ailments. 

“Genetic engineering will ultimately be exploited to ‘enhance’ human capabilities and characteristics, and change our evolutionary trajectory. This, coupled with ‘Augmented’ vs ‘Artificial’ Intelligence (powered by quantum computers in 5-8 years), will make the Industrial Revolution (and the Luddite reaction) look like child’s play. And it will upend Darwinian evolution (e.g. mutation, adaptation, natural selection over millennia) as we have known it.”  

The Yale Stem Cell Center is located at 10 Amistad St.