Testing in mice first

To look for a better option, the researchers grew organoids — small lab-made clusters of tissue that act like miniature organs — from human stem cells. These organoids contained cells capable of producing ACTH. The team first transplanted them into mice whose pituitary glands had been removed.

"The organoids were transplanted just under the skin, in fat or muscle tissue. They produced ACTH for more than six months and clearly extended the lifespans of these mice compared to those that did not receive the transplant. No unwanted tumors or unusual cell growth were observed," said first author Tatsuma Kondo, a guest researcher at Nagoya University's Graduate School of Medicine.

A step toward humans

The researchers then moved closer to human application by transplanting the organoids into a macaque monkey without a pituitary gland. Because the tissue came from a different species, they used immune-suppressing drugs — the same kind already used in transplants of human insulin-producing cells for diabetes — to prevent rejection.

The transplant worked for six weeks. During that time, ACTH and cortisol levels in the monkey's blood rose, and significant weight loss caused by the hormone deficiency slowed. Three months later, tissue samples still contained surviving transplanted cells, although strong immune rejection, which is common in cross-species transplants, limited how well the graft functioned over time.

Stem cell therapies carry a known risk: transplanted cells can migrate from the implant site and grow uncontrollably elsewhere in the body. The researchers checked the monkey's lungs and liver for signs of stray organoid tissue and found none.

Early days

The findings are promising but preliminary. The primate experiment involved a single animal, and the tissue functioned for six weeks — far shorter than the more than six months seen in mice, largely because of cross-species immune rejection. Human-to-human transplants, if they ever happen, would face a weaker form of that problem.

"We tested this approach in a single primate and are planning further studies to improve how long the tissue lasts and test safer immune-suppressing methods," Kondo said.

The study, titled "Functional analysis of adrenocorticotropic-hormone-producing pituitary cells derived from human pluripotent stem cells in murine and primate models of hypopituitarism," appears in Stem Cell Research & Therapy (2026), DOI: 10.1186/s13287-026-05098-y.