Modeling skeletal dysplasia in Hurler syndrome using patient-derived bone marrow osteoprogenitor cells

• DOI: 10.1172/jci.insight.173449
• Publication Date: 2024-03-13T13:16:17Z
• Authors: Samantha Donsante; Alice Pievani; Biagio Palmisano; Melissa Finamore; Grazia Fazio; Alessandro Corsi; Andrea Biondi; Shunji Tomatsu; Rocco Piazza; Marta Serafini; Mara Riminucci
• Keywords: Endochondral ossification; Fibrodysplasia Ossificans Progressiva; Bone remodeling

Dysostosis multiplex is a major cause of morbidity in Hurler syndrome (mucopolysaccharidosis type IH [MPS IH], OMIM #607014) because currently available therapies have limited success its prevention and reversion. Unfortunately, the elucidation skeletal pathogenesis MPS by difficulties obtaining bone specimens from pediatric patients poor reproducibility animal models. Thus, application experimental systems that can be used to dissect cellular molecular mechanisms underlying phenotype identify effective highly needed. Here, we adopted vitro/in vivo based on patient-derived marrow stromal cells generate cartilaginous pellets rudiments. Interestingly, observed heparan sulphate accumulation compromised remodeling cartilage into other tissues critical aspects endochondral ossification process. We also noticed hypertrophic was characterized dysregulation signaling pathways controlling hypertrophy fate, extracellular matrix organization, glycosaminoglycan metabolism. Our study demonstrates pellet–based system valuable tool dysostosis develop new therapeutic approaches for this hard-to-treat aspect disease. Finally, our approach may applied modeling genetic disorders.