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Nerve cells are not just nerve cells. Depending on how finely we distinguish, there are several hundred to several thousand different types of nerve cell in the human brain according to the latest calculations. These cell types vary in their function, in the number and length of their cellular appendages, and in their interconnections. They emit different neurotransmitters into our synapses and, depending on the region of the brain – for example, the cerebral cortex or the midbrain – different cell types are active.

When scientists produced nerve cells from stem cells in Petri dishes for their experiments in the past, it was not possible to take their vast diversity into account. Until now, researchers had only developed procedures for growing a few dozen different types of nerve cell in vitro. They achieved this using genetic engineering or by adding signalling molecules to activate particular cellular signalling pathways. However, they never got close to achieving the diversity of hundreds or thousands of different nerve cell types that actually exists.

Neurons derived from stem cells are frequently used to study diseases. But up to now, researchers have often ignored which precise types of neuron they are working with.”

Barbara Treutlein, Professor, Department of Biosystems Science and Engineering at ETH Zurich, Basel

However, this is not the best approach to such work. “If we want to develop cell culture models for diseases and disorders such as Alzheimer’s, Parkinson’s and depression, we need to take the specific type of nerve cell involved into consideration.”

Systematic screening was the key to success

Treutlein and her team have now successfully produced over 400 different types of nerve cell. In doing so, the scientists have paved the way for more precise basic neurological research with cell culture experiments.

The ETH researchers achieved this by working with a culture of human induced pluripotent stem cells that had been generated from blood cells. In these cells, they used genetic engineering to activate certain neuronal regulator genes and treated the cells with various morphogens, a special class of signalling molecules. Treutlein and her team took a systematic approach, using seven morphogens in different combinations and concentrations in their screening experiments. This resulted in almost 200 different sets of experimental conditions.

Morphogens

Morphogens are messengers that are known from research into embryonic development. They are not distributed uniformly within an embryo but occur in a variety of concentrations forming spatial patterns. In this way, they define the position of cells within the embryo, for example whether a cell is near the body axis or in the back, abdomen, head or torso. Accordingly, morphogens help to determine what grows where in the embryo.

The researchers used various analyses to prove that they had produced over 400 different types of nerve cell in their experiment. They examined the RNA (and therefore genetic activity) at the level of individual cells, as well as the external appearance of cells and their function: for example, which type of cell appendage they had in which quantities and which electric nerve impulses they emitted.

The researchers then compared their data with information from databases of neurons from the human brain. By doing this, they were able to identify the types of nerve cell that had been created, such as those found in the peripheral nervous system or brain cells and the part of the brain they come from, whether they perceive pain, cold or movement, and so on.

In-vitro neurons for active ingredient research

Treutlein clarifies that they are still a long way off producing all types of nerve cell that exist in vitro. Nonetheless, the researchers now have access to a much larger number of different cell types than they had before.

They would like to use in-vitro nerve cells to develop cell culture models for studying serious neurological conditions, including schizophrenia, Alzheimer’s, Parkinson’s, epilepsy, sleep disorders and multiple sclerosis. Cell culture models of this kind are also of great interest in pharmaceutical research for testing the effects of new active compounds in cell cultures without animal testing, with the ultimate aim of one day being able to cure these conditions.

In the future, the cells could also be used for cell replacement therapy, which involves replacing sick or dead nerve cells in the brain with new human cells.

But there is a challenge to overcome before this can happen: the researchers often produced a mixture of multiple different types of nerve cell in their experiments. They are now working to optimise their method so that each experimental condition only produces one specific cell type. They already have some initial ideas as to how this might be achieved.

A retrospective study analyzing over 2 decades of national data found that while overall US neonatal mortality from perinatal causes has declined, mortality from slow fetal growth and fetal malnutrition has increased annually, highlighting persistent disparities in neonatal outcomes.^1,2

The study, led by Khan et al, utilized data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) between January 1, 1999, and December 31, 2022. Researchers focused on neonatal deaths due to perinatal complications, defined using International Classification of Diseases, Tenth Revision (ICD-10) codes P00 to P96. Standardized diagnostic groupings from the National Center for Health Statistics were used to identify and stratify the 10 leading causes of neonatal death over the study period. Mortality rates were further analyzed by sex, delivery method, birthplace, and age at death. Joinpoint regression modeling was used to assess trends, with statistical significance set at P < .05.

A total of 283,696 neonatal deaths were reported during the study period, with males accounting for 56.2% (n = 159,445) of deaths. The top 10 causes represented 79.8% (n = 226,323) of all deaths. The leading cause was disorders related to short gestation and low birth weight, with a crude mortality rate (CR) of 102.10 per 100,000 live births. Other major contributors included maternal complications of pregnancy (CR, 37.71), complications of the placenta, cord, and membranes (CR, 23.39), and bacterial sepsis of the newborn (CR, 15.88).

Most causes showed a significant decline over time. The largest reduction was observed in deaths due to interstitial emphysema and related conditions, with an annual average percent change (AAPC) of −5.40% (95% CI, −6.20% to −4.64%). Mortality from respiratory distress originating in the perinatal period also declined significantly (AAPC, −3.63%; 95% CI, −4.45% to −3.00%).

Conversely, mortality from slow fetal growth and fetal malnutrition rose by 1.91% per year (95% CI, 0.46% to 3.82%). Mortality rates related to maternal complications (AAPC, −0.35%; 95% CI, −1.04% to 0.29%) and bacterial sepsis (AAPC, −0.24%; 95% CI, −0.57% to 0.14%) remained statistically stable over time.

According to the authors, “US neonatal mortality has generally decreased, likely due to medical advancements, improved prenatal care, and neonatal intensive care interventions.” However, they noted that the rise in deaths from malnutrition “may reflect impaired prenatal nutrition.”

Disparities were also noted by sex and delivery method. Male neonates consistently experienced higher mortality, possibly due to “differences in lung development and immune response.” Vaginal deliveries were associated with nearly three times the mortality rate of cesarean deliveries, which may be linked to complications such as “birth trauma and prolonged labor.”

Additionally, sepsis-related deaths were most common between days 1 and 28 of life, often associated with prematurity. While deaths from interstitial emphysema declined in hospital births, births occurring outside of hospital settings had a higher risk of neonatal death, likely due to “inadequate delivery management.”

The study authors acknowledged several limitations, including the inability to assess key nutritional exposures such as breastfeeding, exclusion of congenital malformations to focus on perinatal causes, and limitations related to assigning a single ICD-10 code per death, which may not capture coexisting conditions. “Some ICD-10 blocks grouped pathophysiologically distinct conditions… which may affect interpretation,” the authors wrote. The transition between versions of the US Standard Certificate of Live Birth across states also posed challenges in data consistency during earlier years of the study.

The authors concluded that while progress in neonatal mortality reduction is evident, targeted strategies are needed to address persistent risks associated with fetal malnutrition, delivery practices, and nonhospital births.

References:

1. Khan M, Nabi W, Aziz N, et al. US Neonatal Mortality From Perinatal Causes. JAMA Pediatrics. Published online June 23, 2025. doi:https://doi.org/10.1001/jamapediatrics.2025.1710
2. Centers for Disease Control and Prevention. Maternal and infant health: an overview. CDC. 2024. Accessed July 11, 2025. https://www.cdc.gov/maternal-infant-health/about/index.html

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