Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I.

Abstract

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases.

• Authors: Isabella Azario, Alice Pievani, Federica Del Priore, Laura Antolini, Ludovica Santi, Alessandro Corsi, Lucia Cardinale, Kazuki Sawamoto, Francyne Kubaski, Bernhard Gentner, Maria Ester Bernardo, Maria Grazia Valsecchi, Mara Riminucci, Shunji Tomatsu, Alessandro Aiuti, Andrea Biondi, Marta Serafini
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 9473 (08 25 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28842642 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Cord Blood Stem Cell Transplantation (methods)
• Disease Models, Animal
• Dysostoses (diagnostic imaging, etiology, pathology, therapy)
• Female
• Hematopoietic Stem Cells (cytology, metabolism)
• Mice
• Mucopolysaccharidosis I (metabolism, pathology, therapy)
• Pregnancy
• Treatment Outcome
• X-Ray Microtomography