Scientists reveal hidden world of living cells in human milk

Advanced nanoscale imaging technology has revealed the diversity of living cells in human milk and uncovered new insights into how these cells are structured, what they contain and how they use nutrients.

Biomedical scientists at The University of Western Australia co-authored the study published in ACS Nano, which provides a new view of the cellular and metabolic complexity of human milk by combining correlative imaging, stable isotope tracing and single-cell analysis.

Lead author PhD candidate Qiongxiang (Lynn) Lin said human milk is an incredibly complex biological system containing many different types of living cells, yet we still know relatively little about what the cells do.

“With our new approach, we can look inside individual cells at the nanoscale and begin to understand how their structure, chemical composition and metabolism are connected,” Ms Lin said.

Researchers examined major cell populations found in human milk, including milk-producing cells, known as lactocytes, and different types of immune cells such as neutrophils, macrophages and dendritic cells.

The team combined confocal and electron microscopy with nanoscale secondary ion mass spectrometry (NanoSIMS) to characterise the cellular identity, ultrastructure and chemical composition of individual human milk cells in detail.

“Using stable isotope tracing, we found cells in human milk use nutrients in very different ways,” Ms Lin said. “For example, when we tracked where sugar (glucose) ended up, we found it was being turned into fat droplets inside macrophages in milk, and those cells were switching on genes involved in handling fat.

“When we tracked the building blocks of protein (amino acids), we found groups of milk-making cells, known as lactocytes, were especially busy: producing milk, releasing protein, and using energy and fat.”

Professor Donna Geddes, Director of UWA’s Centre for Human Lactation Research and Translation, said the results show human milk cells have distinct functions to enable optimal milk composition and volume.

“The study also revealed high levels of sulphur and iron within immune cells called neutrophils that contribute to the killing of bacteria and help protect babies from infection,” Professor Geddes said.

The team integrated the imaging findings with single-cell RNA sequencing, to allow researchers to connect what individual cells looked like and how they used nutrients.

Dr Kai Chen, from UWA’s School of Biomedical Sciences, said the approach provided a new way to explore the biology of human milk compared to traditional methods.

“By bringing together imaging, metabolic tracing and single-cell analysis, we can connect cell identity with structure and function in ways that were previously difficult to achieve,” Dr Chen said.

Associate Professor K. Swaminathan Iyer, Director of the ARC Training Centre for Biomedical Analysis, said the platform could be used to investigate how human milk cells vary between individuals, throughout lactation and under different maternal health conditions.

“We are particularly interested in understanding whether conditions such as gestational diabetes alter the cellular and metabolic characteristics of human milk,” Associate Professor Iyer said.

“Ultimately, this could help us better understand the biological roles of living cells in human milk and their potential importance for maternal and infant health.”

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