This vision is now moving closer to reality. Three years ago, Tel Aviv University researchers succeeded in engineering a human spinal cord in the lab for the first time. Since then, progress has been rapid, with animal trials showing unprecedented success. Now, for the first time, the technology is set to be tested in human patients.

Prof. Tal Dvir, of TAU’s Sagol Center for Regenerative Biotechnology, head of TAU’s Jan Koum Center for Nanoscience and Nanotechnology, and Chief Scientist of the biotech company Matricelf, explains:
“The spinal cord is made up of nerve cells that transmit electrical signals from the brain to every part of the body. When the spinal cord is torn due to trauma — from a car accident, a fall, or a battlefield injury — this chain is broken. Think of it like an electrical cable that’s been cut: if the two parts don’t touch, the electrical signal can’t pass. The cable won’t carry electricity, and in the same way, the person can’t transmit the signal beyond the site of the injury.”

This is one of the few injuries in the human body with no natural ability to regenerate. “Neurons are cells that do not divide and do not renew themselves. They are not like skin cells, which can repair themselves after injury. They are more similar to heart cells: once damage occurs, the body cannot restore them,” notes Prof. Dvir.

Engineering a Personalized Implant

To overcome this challenge, the TAU researchers developed a fully personalized process. Blood cells are taken from the patient and reprogrammed through genetic engineering to behave like embryonic stem cells, capable of becoming any type of cell in the body.

Meanwhile, fat tissue from the same patient is used to extract substances such as collagen and sugars. These are used to produce a unique hydrogel. “The beauty of this gel is that it’s also personalized, just like the cells. We take the cells that we’ve reprogrammed into embryonic-like stem cells, place them inside the gel, and mimic the embryonic development of the spinal cord,” says Prof. Dvir.

The result is a complete three-dimensional implant. “At the end of the process, we don’t just turn the cells into motor neurons — because cells alone won’t help us — but into three-dimensional tissue: neuronal networks of the spinal cord. After about a month, we obtain a 3D implant with many neurons that transmit electrical signals. These 3D tissues are then implanted into the damaged area.”

Visualization of the next stage of the research – human spinal cord implants for treating paralysis (Photo: Sagol Center for Regenerative Biotechnology)

From Animals to Human Patients

The researchers first tested the implant in lab animals. “We showed that we can treat animals with chronic injuries. Not animals that were injured just recently, but those we allowed enough time to pass — like a person more than a year after an injury. More than 80% of the animals regained full walking ability,” Prof. Dvir explains.

Encouraged by these results, the team submitted the findings to Israel’s Ministry of Health. “About six months ago we received preliminary approval to begin compassionate-use trials with eight patients. We decided, of course, that the first patient would be Israeli. This is undoubtedly a matter of national pride. The technology was developed here in Israel, at Tel Aviv University and at Matricelf, and from the very beginning it was clear to us that the first-ever surgery would be performed in Israel, with an Israeli patient.” he says.

Looking Ahead

The first implant in a human patient is expected within about a year. For the initial trials, the team will focus on patients whose paralysis is relatively recent — within about a year of injury. “Once we prove that the treatment works — everything is open, and we’ll be able to treat any injury,” says Prof. Dvir.

Behind the initiative are key figures from both academia and industry. Prof. Dvir founded Matricelf in 2019 together with Dr. Alon Sinai, based on the revolutionary organ engineering technology developed at TAU under a licensing agreement through Ramot, the University’s technology transfer company. The company’s CEO is Gil Hakim, while the scientific development is led by Dr. Tamar Harel-Adar and her team.

“They managed to get us to the stage of regulatory approvals so quickly — and that’s amazing,” says Prof. Dvir.

Gil Hakim, CEO of Matricelf , concludes: “This milestone marks the shift from pioneering research to patient treatment. For the first time, we are translating years of successful preclinical work into a procedure for people living with paralysis. Our approach, using each patient’s own cells to engineer a new spinal cord, eliminates key safety risks and positions Matricelf at the forefront of regenerative medicine. If successful, this therapy has the potential to define a new standard of care in spinal cord repair, addressing a multi-billion-dollar market with no effective solutions today. This first procedure is more than a scientific breakthrough, it is a value-inflection point for Matricelf and a step toward transforming an area of medicine long considered untreatable. We are proud that Israel is leading this global effort and are fully committed to bringing this innovation to patients worldwide.”

A Window into Human Evolution

The study was led by Prof. Israel Hershkovitz of the Gray Faculty of Medical and Health Sciences at Tel Aviv University and Anne Dambricourt-Malassé of the French National Centre for Scientific Research. The findings of this historic discovery were published in the journal l’Anthropologie.

“Genetic studies over the past decade have shown that these two groups exchanged genes,” explains Prof. Hershkovitz. “Even today, 40,000 years after the last Neanderthals disappeared, part of our genome—2 to 6 percent—is of Neanderthal origin. But these gene exchanges took place much later, between 60,000 to 40,000 years ago. Here, we are dealing with a human fossil that is 140,000 years old. In our study, we show that the child’s skull, which in its overall shape resembles that of Homo sapiens—especially in the curvature of the skull vault—has an intracranial blood supply system, a lower jaw, and an inner ear structure typical of Neanderthals.”

The skull of Skhul I child showing cranial curvature typical of Homo sapiens

Rewriting the Timeline

For years, Neanderthals were thought to be a group that evolved in Europe, migrating to the Land of Israel only about 70,000 years ago, following the advance of European glaciers. In a groundbreaking 2021 study published in the prestigious journal Science, Prof. Hershkovitz and his colleagues showed that early Neanderthals lived in the Land of Israel as early as 400,000 years ago. This human type, which Prof. Hershkovitz called “Nesher Ramla Homo” (after the archaeological site near the Nesher Ramla factory where it was found), encountered Homo sapiens groups that began leaving Africa about 200,000 years ago—and, according to the current study’s findings, interbred with them. The child from the Skhul Cave is the earliest fossil evidence in the world of the social and biological ties forged between these two populations over thousands of years. The local Neanderthals eventually disappeared when they were absorbed into the Homo sapiens population, much like the later European Neanderthals.

The lower jaw of Skhul I child showing features characteristics of Neanderthals

Advanced Analysis Confirms Hybrid Traits

The researchers reached these conclusions after conducting a series of advanced tests on the fossil. First, they scanned the skull and jaw using micro-CT technology at the Shmunis Family Anthropology Institute at Tel Aviv University, creating an accurate three-dimensional model from the scans. This enabled them to perform a complex morphological analysis of the anatomical structures (including non-visible structures such as the inner ear) and compare them to various hominid populations. To study the structure of the blood vessels surrounding the brain, they also created an accurate 3D reconstruction of the inside of the skull.

“The fossil we studied is the earliest known physical evidence of mating between Neanderthals and Homo sapiens,” says Prof. Hershkovitz. “In 1998, a skeleton of a child was discovered in Portugal that showed traits of both of these human groups. But that skeleton, nicknamed the ‘Lapedo Valley Child,’ dates back to 28,000 years ago—more than 100,000 years after the Skhul child. Traditionally, anthropologists have attributed the fossils discovered in the Skhul Cave, along with fossils from the Qafzeh Cave near Nazareth, to an early group of Homo sapiens. The current study reveals that at least some of the fossils from the Skhul Cave are the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

Prof. Israel Hershkovitz

In this study, researchers identified the protein TSLP as a trigger for the disease’s development, and found that neutralizing it may significantly ease symptoms.

The study, led by Prof. Ariel Munitz and doctoral student Anish Dsilva from the Gray Faculty of Medical and Health Sciences, was conducted in collaboration with Dr. Chen Varol of Ichilov Hospital, Prof. Marc Rothenberg of Cincinnati Children’s Hospital, and the pharmaceutical company AstraZeneca.  It was supported by grants from the Israel Science Foundation, the US-Israel Binational Science Foundation, and the Azrieli Foundation Canada–Israel. The article was published in Allergy, the leading journal in clinical immunology.

Understanding the Disease

Prof. Munitz explains: “Eosinophilic Esophagitis, or EoE, is a type of food allergy. It is a chronic inflammation of the esophagus caused by an abnormal immune response to food — mainly milk, eggs, wheat, nuts, fish, and more. The disease is characterized by an accumulation of eosinophils, a type of white blood cell that is not typically present in a healthy esophagus. EoE is often associated with other allergic conditions such as asthma and atopic dermatitis. It causes difficulty swallowing, food getting stuck in the esophagus, chest and abdominal pain, and growth delays in children. Current treatments require restrictive diets, and in severe cases, patients rely on essential amino acid formulas. Over the past decade, there has been a concerning rise in the prevalence of EoE worldwide, including in Israel. We are studying the disease in depth to understand the involvement of various immune system components in its progression. These components may serve as targets for future treatment for this disease, and for other allergic disorders as well.”

A previous study from Prof. Munitz’s lab, also published in Allergy, presented an experimental model that closely mimics the course and symptoms of EoE in humans. As a direct continuation of that study, the researchers now focused on a specific aspect of the disease, aiming to understand the role of epithelial cells. Prof. Munitz elaborates: “Epithelial cells form a protective outer layer that prevents foreign bodies from entering organs, including the digestive and respiratory systems. In allergic conditions, epithelial cells release various substances in response to encountering an allergen, and these substances trigger the chain of events that initiate the inflammatory process we experience as an allergy attack.”

TSLP: The Central Player

The researchers found that epithelial cells in the esophagus of the EoE experimental model secreted high levels of two proteins: IL-33 and TSLP. They also discovered that the esophageal tissue contained immune cells with receptors for both proteins, indicating  that these are active proteins capable of initiating the disease.

They then examined whether each protein had a distinct role or acted together. Using genetic engineering, they created models lacking one of the proteins.

The results were clear: removing IL-33 did not change the disease course, but removing TSLP led to a dramatic improvement — in some cases preventing the disease entirely. Similarly, neutralizing TSLP with an antibody caused a significant reduction in symptoms. Sequencing and bioinformatic analyses confirmed that TSLP acts as a master regulator of EoE, making it a promising therapeutic target.

Prof. Munitz concludes: “In this study, we found that the TSLP protein is a central player in EoE — a disease that causes significant suffering and is becoming increasingly prevalent worldwide. We know that pharmaceutical companies are currently developing a variety of antibodies targeting disease-causing proteins, under the broad category of biological therapies, including antibodies against TSLP. We believe these antibodies could serve as an effective treatment for EoE.”

The study was led by Prof. Moran Rubinstein and Prof. Karen Avraham, Dean of the Faculty. Other participants included students Mor Yam, Julan Nasir, Daniel Gelber, Shir Kavin, Roni Gal, Mor Ovadia, Mor Bordinik-Cohen, and Eden Peled — all from the Gray Faculty of Medical and Health Sciences at Tel Aviv University or the Sagol School of Neuroscience — as well as Dr. Moran Heusman-Kedem and Prof. Aviva Fattal-Valevski from the Pediatric Neurology Institute at Dana-Dwek Children’s Hospital, Tel Aviv Medical Center, and Prof. Christopher McKinnon and Prof. Wayne Frankel from Columbia University in the United States.

Prof. Avraham explains: “We were approached by the parents of an Israeli child named Adam, now 8 years old, who is one of approximately 40 people worldwide suffering from an extremely rare genetic disease. It’s a mutation in a gene called GRIN2D, which causes developmental epilepsy, severe delays in motor and cognitive development, and sometimes even premature death.”

Eden Maimon Benet, Adam’s mother, adds: “At Tel Aviv University, we met a remarkable all-women team that took on the mission: to find a cure for our son. I believe the fact that they got to know Adam and our family personally only deepened their dedication and commitment. When Adam was two years old, we embarked on this long journey together — and today, we can already see real light at the end of the tunnel.”

How Do You Study a Disease No One Understands?

In the first stage, the researchers aimed to better understand the disease’s characteristics. To do so, they created a mouse model with a mutation similar to that found in human patients. However, due to the severity of the disease, most of the mice did not survive their first weeks of life — before any meaningful research observations could be made. This led the team to conclude that while the model mimics the human disease, it poses a major challenge: too few mice could be generated for scientific study.

To overcome this, they used genetic engineering tools to create a strain of mice that carry the mutation but do not develop symptoms. These serve as carriers, with half of the offspring born healthy and the other half born with the disease. The affected mice exhibited symptoms similar to those seen in children with the disease. Most lived only a few weeks, and only a few survived up to three months. The researchers observed their behaviour and development at four key stages: at two weeks old (infancy), three weeks (when mice transition to solid food — roughly equivalent to a one-year-old child), four weeks (roughly age six in children), and five weeks (the onset of sexual maturity).

“Because the disease is so rare, we don’t yet fully understand how it progresses with age,” Prof. Rubinstein says. “The mouse model helped us characterize symptoms at various stages. The tests we conducted revealed interesting findings: neurological symptoms — including epilepsy, hyperactivity, and severe motor impairments — appeared as early as infancy. Cognitive impairments, on the other hand, showed up later and worsened gradually. In addition, their lifespan was short — most of the affected mice did not survive to sexual maturity.”

What Happens in the Brain?

In a follow-up experiment, the researchers monitored communication between neurons in the brains of the model mice, focusing on the cerebellum — the brain region responsible for motor control. The tests showed that by just two weeks of age, pathological changes were already present, expressed as reduced neuronal activity. Later in life, activity levels returned to normal; however, the communication between neurons became impaired. Finally, the researchers identified structural changes in the neurons themselves. All these findings help shed light on the mechanism driving the disease.

EEG recordings conducted on the affected mice revealed a unique brain activity pattern that also characterizes the disease in humans. “In most types of epilepsy, seizures are caused by disruptions in brain activity, but between seizures, brain activity is relatively normal,” explains Prof. Rubinstein. “In this disease — in both children and mice — brain activity is consistently disrupted. Moreover, using specific markers we developed, we identified the same abnormal parameters in both mice and humans — a finding that most clearly demonstrates the validity of the model.”

From Testing to Treatment

After confirming that the mouse model accurately mimics the human disease, the researchers began testing the effects of various drugs on the progression of symptoms. They found that ketamine — a drug previously proposed for treating this condition — actually worsened the seizures. In contrast, memantine, another drug currently used for this disease, led to partial improvement in brain function. The same was true for phenytoin, an anti-seizure medication, which also improved some markers of brain activity.

New Hope for Rare Disease Patients

“Modeling the disease using a mouse model is a key tool in making clinical decisions for treating rare diseases,” explains Dr. Heusman-Kedem, who adds: “The model allows us to test the efficacy of known drugs, as well as the safety and effectiveness of innovative treatments — before administering them to patients. For example, the results found in the mouse model helped clarify that memantine may help prevent seizures. Using a mouse model provides critical insights for developing new treatment strategies for rare diseases, where the number of patients is too small to establish broad statistical conclusions. In such cases, animal studies can offer major breakthroughs and support the development of personalized medicine.”

“In this study, we created a mouse model of a rare genetic disease caused by a mutation in the GRIN2D gene,” concludes Prof. Rubinstein. “The model allowed us to better understand how the disease progresses and to test the effectiveness of several existing drugs. We’re now continuing the research and exploring additional therapies — both pharmaceutical and genetic — and we’ve reached promising results, including improvements in cognition and motor function and increased lifespan in the affected mice. We sincerely hope our work brings hope and real progress to families and children battling this rare and devastating disease — and to those affected by other brain conditions with similar mechanisms.”

The kidney grew and developed over months, allowing researchers to see the development of the organ in real time, isolate genes that lead to birth defects, develop new treatments in the field of regenerative medicine, and test the toxicity of drugs during pregnancy on fetal kidneys.

The current model has matured and stayed stable for over half a year. Previous kidney organoids mimicking development broke down within four weeks. This allows long-term research and medical testing on kidney models.

It is also the purest kidney organoid ever developed, with no cross contamination from stem cell development. Previous models using pluripotent stem cells would develop other cellular structures due to the unstable nature of the stem cells. The new organoid only expresses kidney cells, allowing for clear cause-and-effect experiments.

Behind the Breakthrough

The groundbreaking study was led by Prof. Benjamin Dekel, Director of the Sagol Center for Regenerative Medicine at Tel Aviv University and  Director of the Pediatric Nephrology Unit and the Stem Cell Research Institute at the Safra Children’s Hospital at Sheba Medical Center. Also participating in the study were doctoral student Dr. Michael Namestannikov, a graduate of the Physician-Researcher track at the Gray Faculty of Medical and Health Sciences at Tel Aviv University, and Dr. Osnat Cohen-Sontag, a research associate at Sheba Medical Center, as part of Prof. Dekel’s research group. The study was published in the prestigious medical publication The EMBO Journal.

“Life begins with pluripotent stem cells, which can differentiate into any cell in the body,” explains Prof. Dekel. “In the past, they were able to grow organoids – 3D organ-like cultures – by producing such general stem cells and sorting them into kidneys, but after about a month the kidney in culture died, and the process had to be started again. About a decade ago, my research group was able to isolate for the first time the human kidney tissue stem cells that are responsible for the growth of the developing organ. Now we have succeeded for the first time in growing a human kidney in the form of an organoid from the specific stem cells of the kidney, and this in parallel with the maturation process in the uterus that occurs until the 34th week of pregnancy.”

Human fetal kidney cells

Opening Doors to Future Therapies

Researchers grow organoids in laboratory conditions to study organs in ways that are not possible in humans, but organoids derived from pluripotent stem cells often contain unwanted cells unrelated to the organ being studied that contaminate experiment data. Prof. Dekel’s organoid grew from kidney tissue stem cells in a “clean” manner, since these stem cells differentiate exclusively into kidney tissue. These cells developed into different types of kidney cells, and over half a year formed different tissues of the kidney, such as blood filter cells and kidney and urinary ducts, a process known as tubulogenesis.

“Growing the fetal kidney structures can shed new light on biological processes in general, and in particular on processes that lead to kidney diseases,” says Prof. Dekel. “And indeed, when we selectively blocked a certain signaling pathways [in the organoid], we saw how it lead to a birth defect. We are actually seeing live how a developmental problem leads to kidney diseases that are seen in the clinic, which will enable the development of innovative treatments.”

The implications that go far beyond research. “The fact that we can grow kidney tissue stem cells outside the body over time opens the door to regenerative medicine, that is, transplanting kidney tissue grown in the laboratory – inside the body or alternatively harnessing signals the organoid secrets for repair and rejuvenation of a damaged kidney ,” said Prof. Dekel. “We now have an essentially inexhaustible source of different kidney cells, and a better understanding of their different roles in kidney development and function.”

Breakthroughs like this represent Israel’s unique place in the world, says Prof. Dror Harats, Chairman of the Sheba Research Authority. “In recent years, we have witnessed attempts to distance Israel from international centers of influence, and scientific successes of this kind are a reminder that our contribution to medical and scientific research is significant and unquestionable.”