Patient-derived vascularized skin organoids unravel the role of systemic sclerosis fibroblasts in microvascular dysfunction.
PITAVAL, A.; JOBEILI, L.; WELSCH, C.; COMBE, S.; PAPOZ, A.; GIBOT, L.; ROUSTIT, M.; CRACOWSKI, J.-L.; COUTTON, C.; GIDROL, X.; RACHIDI, W.
Show abstract
Systemic sclerosis (SSc) is a complex and poorly understood disease affecting connective tissue. Patients with SSc may suffer from painful digital ulcers due to endothelial cell dysfunction and excessive extracellular matrix production through fibroblast activation, leading to skin fibrosis. To better understand the crosstalk between fibroblasts and endothelial cells in the context of SSc, we developed 3D vascularized skin organoids using SSc-derived fibroblasts from two patients. After several morphological and molecular characterizations of healthy and pathological skin organoids, we demonstrate, for the first time, that SSc patient-derived fibroblasts can trigger structural abnormalities in skin organoids that emulate some features of the disease: the vasculopathy characterized by the formation of giant capillaries and the early fibrosis associated with cytokine and chemokine secretions. It appeared that SSc-derived fibroblasts play a major role in the vascular specificities of this disease, highlighting an interesting crosstalk between these cell populations. Therefore, these SSc-fibroblast containing skin organoids may enable to gain a deeper insight into the physiopathology of SSc and provide an alternative model to animal testing to evaluate the efficacy and safety of new drugs.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.