In a lab at the Hubrecht Institute in the Netherlands, scientists have coaxed tiny clumps of cells into an astonishing form: an organoid that mirrors the human fetal pancreas. This remarkable creation, detailed today in Cell, represents a complete version of the pancreas in its early development. It features all three major cell types—acinar, ductal, and endocrine—and, for the first time, reveals a stem cell capable of giving rise to all of them.

For decades, researchers have struggled to reconstruct the pancreas’s intricate biology in a dish. This new model could offer a clearer window into how the pancreas forms, how it functions, and how it goes wrong, potentially opening doors to new treatments for diseases like diabetes and pancreatic cancer.

Rebuilding the Pancreas in Miniature

The pancreas is one of the body’s unsung heroes. Perched in the abdomen, this spongy, leaf-shaped organ is a multitasker. On one front, it churns out enzymes to digest food. On the other, it manages blood sugar, releasing insulin and other hormones.

Each of these jobs depends on specialized cells. Yet, studying these cells in their native environment has long been a challenge. Researchers have turned to organoids—microscopic versions of organs grown from stem cells—to help. But until now, organoids of the pancreas have been incomplete, often representing just a single type of cell.

Amanda Andersson Rolf, a scientist at the Hubrecht Institute and lead author of the study, set out to change that.

“We wanted to create an organoid that includes all the cell types found in a real pancreas,” she explains. “With such an organoid, we could study how these different cells interact and gain a deeper understanding of how the pancreas develops.”

Andersson Rolf and her colleagues started with fetal tissue from the human pancreas. Using a cocktail of carefully calibrated signals, they coaxed the cells to organize themselves into a three-dimensional structure. To their astonishment, the cells formed not just one type, but all three major types of pancreatic cells. The acinar cells secreted digestive enzymes. The ductal cells formed tubular channels to transport these enzymes. And the endocrine cells produced insulin and other hormones.

“The cells didn’t just appear—they worked,” Andersson Rolf says. “It was like watching a miniature pancreas come to life.”

A Stem Cell Puzzle

As the researchers studied their organoid, they stumbled upon a mystery: a new type of stem cell nestled within the fetal pancreas. This cell, it turns out, can give rise to all three major pancreatic cell types. Andersson Rolf and her team watched as these stem cells multiplied and matured, their descendants forming functional enzymes and hormones.

But the surprises didn’t end there. Comparing their organoids to previous studies of mice, the team noticed a crucial difference. In humans, the fetal pancreas holds onto its stem cells far longer than in mice. And these human stem cells carried a molecular signature—a protein called LGR5—that was absent in mice.

“It’s a vivid reminder of why studying human biology is essential,” Andersson Rolf notes. “We wouldn’t have found this by relying on animal models alone.”

New Frontiers in Pancreas Research

This living model of the fetal pancreas is more than a scientific marvel—it’s a tool with immense potential. By studying these organoids, scientists hope to unravel how genes and the environment shape the pancreas’s development. They could explore how mutations disrupt its formation or how toxins impair its function.

In the future, such research might even lead to regenerative therapies, where damaged pancreatic cells are replaced by lab-grown ones. But Andersson Rolf is cautious.

“We’ve opened a door, but there’s so much more to learn,” she says. “We’re just beginning to understand how these cells and molecules interact, both in health and disease.”

For now, this tiny organoid offers something profound: a glimpse of the human pancreas as it begins to take shape, a feat of biological engineering that brings us closer to understanding the organ’s mysteries—and how to heal it when it falters.