Cutaneous melanoma is one of the most aggressive skin cancers, and its treatment development continues to face significant barriers due to limitations in current preclinical models. Traditional in vivo animal testing, while common, often lacks translational relevance due to the fundamental biological differences between human and animal skin. Furthermore, ethical and regulatory pressures aligned with the 3Rs principles (Replacement, Reduction, Refinement) are increasingly calling for alternative models that reduce animal use. In this context, there is an urgent need for innovative, human-relevant platforms that can bridge the gap between early-stage research and clinical application.
This project proposes the development of SkinModelOma, an ex vivo multicompartmental melanoma graft model designed to mimic human melanoma more accurately. It involves grafting a multicellular 3D spheroid—composed of melanoma cells, keratinocytes, fibroblasts, and monocytes—into human skin tissue. By integrating multiple human skin components and immune cells into a single, living structure, SkinModelOma aims to replicate the complex tumor microenvironment of melanoma more faithfully than any current model.
Through extensive histological and ultrastructural characterization, this model has already demonstrated features resembling in vivo melanoma lesions, such as extracellular matrix deposition, cell clustering, immune cell distribution, and proliferation markers. The successful development and grafting of these spheroids have enabled tissue integration and analysis of tumor-like behavior without the need for live animal models.
Critically, SkinModelOma accounts for biological diversity by incorporating age, gender, and skin type variability, factors that are rarely considered in preclinical testing but are essential for developing personalized therapies. From a strategic and political perspective, this project aligns with the European Union’s commitment to animal welfare, precision medicine, and gender-sensitive research. The development of a validated, human-derived melanoma model has the potential to significantly reduce animal testing, streamline the drug development process, and ultimately deliver more effective therapies to patients faster.
In terms of impact, the project is expected to: (i) Provide a reliable alternative to animal models for melanoma drug testing; (ii) Enhance the predictive accuracy of preclinical studies; (iii) Facilitate the screening of personalized therapies based on human skin diversity; (iv) Strengthen Europe’s leadership in 3D tissue engineering and ethical innovation in biomedicine. Moreover, by promoting an inclusive and human-centered approach to innovation, SkinModelOma stands to make a lasting contribution to both science and society.
