University of Tsukuba researchers delivered embryonic pancreatic cells into mouse fetuses via the placenta and later found donor cells in islets, acinar tissue and ducts, but mice lacking the Pdx1 gene did not grow a recognizable pancreas.
Transplanting cells into a fetus before birth is an attractive idea. A developing embryo is still building its organs, and its immune system has not yet learned to reject foreign tissue. In principle, cells introduced at the right moment might be swept into the body’s own construction program and become part of a working organ.
Researchers at the University of Tsukuba in Japan have been exploring one way to do this, by injecting cells into the placenta of a pregnant mouse so that they reach the fetus. In a new study published in Scientific Reports, they report that pancreatic cells delivered this way were later found in the pancreas of some mice after birth, in tissue types that make up the organ’s main working parts.
The results also come with clear limits. In mice lacking a gene essential for pancreas development, the transplanted cells did not produce a pancreas that could be seen with the naked eye, and the source of some insulin detected in those animals remains unclear.
A route through the placenta
The team had previously developed the intraplacental transplantation method for delivering pancreatic progenitor cells, immature cells that can give rise to the organ’s specialized tissues. In the new work, they took cells from the pancreatic buds of mouse embryos at embryonic day 12.5, a stage when the pancreas is still forming, and transplanted them into recipient embryos at embryonic day 9.5, about three days earlier in development.
Mouse pregnancy lasts roughly three weeks, and the pancreas begins to take shape early. It first appears as small buds growing from the embryonic gut tube, which later fuse and branch into the mature organ. By transplanting slightly more advanced cells into younger embryos, the researchers aimed to place donor cells into an environment where pancreas formation was just getting under way.
Donor cells in all three compartments
After the mice were born, the researchers found donor-derived cells in the pancreas of some recipients. The cells appeared in regions corresponding to the islets, the acinar tissue and the ducts.
Those three compartments carry out the pancreas’s two main jobs. The islets, small clusters of cells scattered through the organ, release hormones including insulin, which lowers blood sugar. Acinar cells, which make up most of the pancreas, produce digestive enzymes, and the ducts carry those enzymes to the intestine. Finding donor cells in all three suggests that the transplanted progenitors were able to take part in building different parts of the organ.
The distribution of donor cells varied from mouse to mouse. The release does not say how many mice received transplants or how many showed donor cells.
Tracking donor cells in experiments like this typically depends on a label that distinguishes them from the recipient’s own cells, such as a fluorescent marker or a genetic tag carried by the donor animal. Researchers can then examine tissue sections under a microscope to see where labeled cells have settled and what kinds of cells they have become.
Testing mice without a pancreas gene
The researchers also tested the approach in mice lacking Pdx1, a gene that is essential for pancreas development. Animals without functional Pdx1 fail to form a normal pancreas, and in humans, mutations in the gene are associated with pancreatic agenesis, a rare condition in which the organ does not develop, as well as with a form of inherited diabetes.
Such mice offer a test of whether donor cells can do more than mingle with existing tissue. If the recipient cannot build a pancreas on its own, any organ that appears would have to come largely from the transplanted cells.
In separate groups of these animals, some transplanted mice showed detectable insulin in their blood or brief rises in blood glucose after birth. But among the Pdx1-deficient recipients for which the team had anatomical records, no organized pancreatic tissue was visible to the naked eye in the region examined.
Because the researchers did not determine where the donor cells ended up in these animals, they cannot say where the insulin came from. As the release puts it, “the source of the detected insulin remains unclear.”
Why build organs before birth?
Diabetes is driven, in most cases, by the loss or failure of insulin-producing beta cells in the islets. Transplants of donor islets can help some patients with type 1 diabetes, but they depend on scarce donated organs and require lifelong drugs to suppress the immune system. Scientists have therefore spent years trying to grow insulin-producing cells from stem cells and to find better ways of getting such cells to settle and function in the body.
Fetal transplantation research also intersects with efforts to treat genetic conditions before birth and with broader studies of how organs assemble during development. Understanding whether and how injected progenitor cells integrate into a growing organ helps clarify which cues guide cells to the right place and what they need to mature.
Next: human-derived stem cells
The team plans to examine how pancreatic progenitor cells derived from induced pluripotent stem cells, or iPSCs, migrate and differentiate after intraplacental transplantation. iPSCs are adult cells reprogrammed into an embryonic-like state, from which they can be coaxed to develop into many cell types, including pancreatic cells.
Moving from mouse embryonic tissue to stem cell-derived cells would be an important step, because iPSCs can be produced in large numbers and, in principle, from a specific individual. Whether such cells behave like natural embryonic progenitors once inside a developing fetus is one of the questions the next experiments are meant to address.
For now, the study establishes that cells delivered through the placenta can reach the developing pancreas and persist after birth, while showing that making a whole new organ in an animal unable to build its own is a much taller order.
Notes
- Javanfekr Shahri, Z., et al. “E12.5 pancreatic bud-derived cells are detected in recipient pancreata after intraplacental transplantation, but Pdx1-deficient recipients lack a macroscopically detectable pancreas.” Scientific Reports, 2026. DOI: 10.1038/s41598-026-65314-w.
- University of Tsukuba. “Pancreatic bud-derived cells delivered through the placenta are detected in the pancreas after birth.” EurekAlert!, 22 October 2026. https://www.eurekalert.org/news-releases/1148812.
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