For the first time, a bone organoid, a three-dimensional reproduction of human cartilaginous and bone tissue, has been created in the laboratory using skeletal stem cells from patients with Hurler syndrome to study the mechanisms and test more effective treatments for this genetic disease rare pediatric disease that affects one in 100,000 children in Europe. The result was achieved thanks to research carried out by the Tettamanti Foundation of Monza and the Sapienza University of Rome, published in the international scientific journal 'Jci Insight'.
The co-authors of the study include Shunji Tomatsu of the University of Delaware (USA), one of the world's leading experts on mucopolysaccharidosis, a group of rare genetic pathologies of which Hurler syndrome is part. This disease is caused by the mutation of a gene and the consequent absence of the enzyme which in the human body is responsible for the 'disposal' of some chains of sugars, called glycosaminoglycans. The accumulation of these molecules damages all organs and tissues, in particular the bones which appear to be the part of the body most resistant to the therapies available today: enzyme replacement, which consists in the administration of the missing enzyme, allogeneic cell transplant hematopoietic stem cells and gene therapy, i.e. the infusion into the patient of the patient's own hematopoietic stem cells, in which the mutated gene has been 'corrected' in the laboratory.
The organoid, which replicates some peculiar characteristics of the bones of patients affected by this pathology, is considered by scientists to be a precious model for observing the mechanisms of the disease with even greater precision and on which to experiment with more effective drugs. “The organoid was created from skeletal stem cells, essential cells for generating bone tissue, taken from the bone marrow of young patients”, explain Marta Serafini of the Tettamanti Foundation of the Irccs San Gerardo dei Tintori of Monza and Mara Riminucci, of the Department of Molecular Medicine of Sapienza University. “These cells generated cartilage which was then transformed into bone tissue and bone marrow in the three-dimensional model. It was observed, also through molecular and histological analyses, that the organoid showed important alterations compared to healthy subjects. The research represents a first important step to deepen the study of this pathology and, in perspective, of other rare genetic diseases with skeletal involvement”.
“It is essential to develop models to study rare diseases given the difficulty of obtaining and, therefore, analyzing tissue samples, particularly from pediatric patients”, observe Serafini and Riminucci.
Hurler syndrome is the most serious form of mucopolysaccharidosis type 1, a rare genetic disease which, in turn, is part of the larger family of mucopolysaccharidoses, characterized by the absence of the enzymes necessary to metabolise and dispose of sugar molecules in cells complex. The accumulation of these molecules damages organs and tissues and is the basis of serious symptoms including growth problems, skeletal deformities, malfunction of internal organs and the nervous system. Bones are particularly resistant to the therapies currently used to treat Hurler syndrome, experts explain, and therefore skeletal deformities are one of the most serious symptoms of this pathology. Studying its mechanisms, also through bone organoids obtained from human cells, increases the possibility of understanding Hurler syndrome more thoroughly and prospectively experimenting with more effective therapies.
“I would like to underline – concludes Andrea Biondi, scientific director of the Irccs San Gerardo dei Tintori – the importance of the results within research on rare diseases and in particular congenital metabolic ones, which has in the new Irccs one of its most relevant areas of research and development from both a clinical and experimental point of view”.
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