Establishment of patient-derived bone organoids to recapitulate and dissect Hurler syndrome's skeletal disease

Mucopolysaccharidosis type I is a disease caused by the mutation of the IDUA gene, encoding the alpha-L-Iduronidase enzyme. Accumulation of glycosamminoglycans (GAGs) due to IDUA deficiency results in a complex skeletal phenotype referred to as dysostosis multiplex. The cellular and molecular pathogenetic mechanisms underlying dysostosis multiplex are still poorly understood. In this study we adopted in vitro and in vivo experimental systems based on patient derived bone marrow stromal cells (BMSC) to generate chondroid and bone rudiments. Transcriptome analysis of chondroid pellet at 5 weeks generated in vitro with BMSCs derived from HD and MPS IH could help to elucidate molecular mechanisms underlying the skeletal phenotype of Hurler Syndrome.