Although pancreatic islet transplantation holds promise for the treatment of type I diabetes, its application has been significantly hampered by transplant rejection. Here, an approach is demonstrated to support trans‐species islet beta cells from a rat to grow and function in the body of a mouse host while overcoming graft rejection. This approach, which builds on remodeling of the mouse testicle by local injection of a tumor homogenate, establishes an immunosuppressive and proregenerative niche in the testicle. This remodeling proves necessary and effective in shaping the testicle into a unique site to accommodate xenograft cells. Rat pancreatic beta cells—from both the insulinoma (cancer cells) and pancreatic islet (normal tissue)—survive, grow, and form a desirable morphology in the remodeled mouse testicle. Notably, when hyperglycemia is induced in the host body, these xenografts secrete insulin to regulate the blood glucose level in mice for as long as 72 days. Furthermore, no graft rejection, acute inflammation, or safety risks are observed throughout the study. In summary, it is demonstrated that the growth of xenogeneic insulinoma cells in a mouse testicle might serve as an alternative approach for islet transplantation.

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In article number 1801694 , Junfeng Zhang, Chunming Wang, Lei Dong, and co‐workers biochemically remodel one of the two testicles of a mouse into a site that can protect xenogeneic islet cells from immune rejection. The transplants, both of primary origin and from a cancer source, can grow and function like a normal islet in the new host body, thus compensating for the glucose‐control function of the incapable pancreas.