A new study from the Center for Research on Ingredient Safety (CRIS) in partnership with Corewell Health shows that a lab model made from human cells can accurately reflect how lead exposure during pregnancy affects a baby’s developing immune system. The study’s approach offers scientists a novel, human-relevant method for examining the effects of chemicals on immune development.
Top Takeaways:
- The study shows that a new cell-based method can further help researchers evaluate the safety of chemical ingredients on the developing human immune system, without using laboratory animals.
- A human cell-based model of immune development accurately mimics the effects of lead exposure on the developing immune system in utero. The validation of cell-based assays to understand human biology is needed, as scientists move away from animal modeling, and the recently published research from CRIS moves this process forward by comparing laboratory results to human exposure to the heavy metal lead.
Background: Lead exposure and health risks.
Lead exposure remains a persistent public health challenge in the United States and around the world.
Lead is a heavy metal known to affect multiple organ systems, including the nervous, renal, and immune systems. During pregnancy, even low levels of exposure can cross the placental barrier, potentially impacting the development of the baby’s immune and nervous systems.
However, scientists have historically relied on animal models to investigate the effects of lead exposure on the developing immune system, with animal models often unable to predict human outcomes accurately.
What did researchers study pertaining to lead exposure?
CRIS researchers, in partnership with Corewell Health, investigated whether a human cell-based model of red blood cell and immune cell formation (hematopoiesis) could replicate the effects of lead exposure observed in human pregnancies.
The team cultured human hematopoietic stem cells (the cells that generate red blood cells and white blood cells) and exposed them to lead (II) acetate at levels comparable to real-world exposures. These results were compared with blood samples collected from pregnant individuals in West Michigan, who enrolled in the study through Corewell Health, to examine maternal lead levels and the effects of lead exposure on the developing immune system, by analyzing the cells present in infant cord blood at delivery.
What did the researchers find?
The study revealed several key findings:
- Lead exposure altered immune cell development. Lead suppressed certain types of myeloid cells, such as monocytes and granulocytes, which play key roles in immune defense.
- Lead increased early B cell formation. Lead exposure accelerated the development of pre–B cells, a finding consistent with previous animal studies.
- The cell-based model matched real-world results. Cord blood from lead-exposed pregnancies showed similar immune shifts with fewer circulating monocytes and early-developing B-cells, which confirms that the lab-based system closely reflects human immune cell development.
Together, these findings show that lead is a potential developmental immunotoxicant, subtly changing how a child’s immune system forms during pregnancy. Over time, these shifts could either resolve or conversely influence how the immune system responds to infections, vaccines, or allergens later in life.
Why does this study matter?
This research highlights the value of New Approach Methodologies (NAMs), which are advanced, non-animal testing systems that use human cells to better predict human health outcomes.
By confirming that a cell-based human stem cell model can replicate real-world exposure effects, this study supports broader regulatory adoption of NAMs to improve chemical safety assessments while reducing reliance on animal models.
The good news.
While lead remains a serious concern, this study represents progress in both public health and scientific innovation. The partnership between Michigan State University and Corewell Health demonstrates how community-engaged research can identify opportunities for collaboration, promoting public health and awareness.
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