Update: Development of advanced human preclinical models for FSHD modeling

Posted by Friends of FSH Research on Nov 23, 2025

Report by Dr. Stefano Testa
See also Development of advanced human preclinical models for FSHD modeling

The aim of this project is to develop advanced human-based skeletal muscle models capable of faithfully reproducing the main features of FSHD and other muscular diseases. These models could become an effective alternative to animal testing, allowing faster and more accurate screening of new therapies.

In the first phase, we created innovative surfaces, produced through a safe laser-based technique, that guide muscle cells to align and mature more efficiently. Using this strategy, we developed human muscle models using cells from healthy donors as well as from patients with FSHD. The healthy models formed long, well-aligned, and mature fibers, while the disease models reproduced characteristic alterations, such as thinner and more branched fibers. Thanks to their high level of organization, these models also allow detailed analysis of individual muscle fibers, offering a powerful tool for studying disease-related changes.

In parallel, we are developing a muscle-on-a-chip system to produce standardized 3D muscle models. The chip uses tiny pillars to guide the muscle cells, helping them form well-structured fibers. In preliminary tests, healthy human muscle cells were successfully cultured on these chips, forming organized 3D muscles that could be easily visualized and characterized at the microscope.

The results so far are very encouraging. The next steps will include applying electrical stimulation to further enhance muscle maturation and assess functionality. Once fully standardized, we will use these models to compare healthy and FSHD-derived muscles, providing a reliable platform to study the disease and test potential therapies.