Nagoya University Researchers Achieve First Primate Human Pituitary Transplant

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“The organoids were transplplemented 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 Tatsuma Kondo.

Researchers in Japan have successfully transplanted lab-grown human pituitary tissue into a primate, restoring critical hormone signals in a breakthrough for lifelong endocrine disorders. Published in the journal Stem Cell Research & Therapy, the study details how mini-organ organoids derived from human stem cells produced adrenocorticotropic hormone, known as ACTH, after being implanted into an animal model whose pituitary gland had been surgically removed.

Anatomy of a Master Gland and Its Failures

The pituitary gland rests at the base of the brain, directing the release of vital hormones that govern growth, metabolism, and stress responses. When disease or surgery damages this gland, patients develop hypopituitarism and lose their ability to produce ACTH, which signals the adrenal glands to release cortisol.

Daily hormone pills serve as the standard treatment. Yet these oral medications fail to match the body’s natural hourly fluctuations. Consequently, patients remain vulnerable to dangerous stress vulnerabilities and an elevated risk of sudden death.

Cultivating Human Organoids in the Laboratory

Led by investigators at Nagoya University, the research team grew small tissue masses called organoids from human stem cells, specifically cultivating cells capable of producing ACTH. The scientists first tested these structures in mice that had their pituitary glands surgically removed, placing the organoids just under the skin or into fat and muscle tissue.

Human Organoids Function in Macaque Monkeys

Following the success in rodents, the research team advanced to a primate model, implanting the human-derived organoids into a macaque monkey whose pituitary gland had also been removed. To counter cross-species immune rejection, the team administered immune-suppressing drugs typically used in human islet cell transplants for diabetes.

The transplanted tissue functioned for six weeks, elevating blood levels of both ACTH and cortisol while slowing the significant weight loss typically caused by the hormone deficiency. Tissue samples collected three months post-transplantation confirmed that surviving cells remained despite aggressive immune barriers.

Researchers Find No Abnormal Growth in Primates

A primary safety concern with stem cell therapies involves stray cells migrating from the transplant site and proliferating uncontrollably elsewhere in the body. To evaluate this risk, the Nagoya University researchers inspected the lungs and liver of the primate subjects for signs of ectopic organoid tissue, finding no abnormal growth.

The team noted that strong immune rejection inherent to cross-species grafting currently limits the longevity of the transplant function. First author Tatsuma Kondo, a guest researcher at the Nagoya University Graduate School of Medicine, stated that the group tested the approach in a single primate and is actively planning subsequent investigations to improve tissue survival times and evaluate safer immunosuppressive protocols.