Cell and tissue xenotransplantation: clinical purpose determines translational strategy and therapeutic endpoints

Solid organ xenotransplantation is moving into early clinical use, whereas living xenogeneic cells and tissues are being developed for distinct therapeutic tasks. Product-based discussions can obscure differences in required functional duration, immune exposure, consequences of product loss, and acceptable treatment burden. This review proposes a purpose-based framework that first defines the clinical task, required functional interval, and consequences of failure, and then uses these factors to guide donor genotype, delivery or implantation, immune management, manufacturing, and endpoint selection. Islets and corneal grafts illustrate durable physiological replacement; hepatocytes used for acute liver failure represent temporary metabolic support; viable porcine skin provides temporary tissue protection; and porcine red blood cells provide emergency oxygen delivery. These categories describe intended use rather than fixed product properties, and the same cell type may require a different translational pathway in another indication. The framework clarifies why graft persistence is essential in some applications but only an enabling measure in others, and why assumptions derived from vascularized organs should not be applied uniformly to cellular and tissue products. A purpose-based approach may improve preclinical study design, product development, endpoint selection, and regulatory evaluation.