Penn Vet Researchers Develop First Lab-Grown Adrenal Organoid That Mimics Human Stress Response And Tissue Complexity

Researchers at Penn Vet have created functional adrenal organoids that produce cortisol, offering a new way to study stress and treat adrenal insufficiency.

By: AXL Media

Published: Mar 31, 2026, 11:23 AM EDT

Source: Information for this report was sourced from University of Pennsylvania

Replicating the Body’s Stress Command Center

The adrenal glands, walnut-sized organs situated above the kidneys, serve as the body's primary source of essential survival hormones, including the "stress hormone" cortisol. Despite their critical role in regulating metabolism and responding to trauma, the early developmental stages of the human adrenal cortex have remained historically difficult to study. Researchers at the University of Pennsylvania School of Veterinary Medicine have now bridged this gap by creating a lab-grown organoid system that faithfully mimics the complex tissue structures and hormonal functions of a developing human adrenal gland.

Step-by-Step Engineering of Complex Tissue

The research team, led by Kotaro Sasaki and Michinori Mayama, utilized human-induced pluripotent stem cells to reconstruct the gland's development. Unlike previous attempts that lacked functional depth, this study identified the specific signaling interactions required between different cell populations to form a layered 3D structure. A key discovery was the role of the adrenal "capsule"—the connective tissue surrounding the gland—which provides the essential chemical cues to establish the progenitor cells responsible for hormone production.

Functional Cortisol Production in a Controlled Setting

The most significant milestone of the new organoid is its proven functionality. When exposed to adrenocorticotropic hormone—the signal the brain typically sends to trigger a stress response—the organoids successfully produced both cortisol and androgens. This ability to respond to external stimuli allows scientists to model how the human body reacts to stress at a molecular level within a controlled laboratory environment, offering an unprecedented look at a biological process that was previously "inaccessible" deep inside the body.