Indeed, in a hybrid human–severe combined immunodeficient (SCID) mouse skin xenotransplant model, we were able to maintain/reconstitute the SSc phenotype using skin biopsies from SSc patients, indicating that the altered balance between inhibitory Smad7 and R-Smads, due to Smad7 deficiency and Smad3 up-regulation, may represent an intrinsic and persistent defect in tissue fibroblasts that can maintain or even induce SSc lesions autonomously in the absence of altered circulatory or systemic factors [9]. Here, SMAD7 is linked to systemic sclerosis.