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Sci Rep. 2017 Aug 25;7(1):9473. doi: 10.1038/s41598-017-09958-9.

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

Author information

1
Dulbecco Telethon Institute, Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Monza, 20900, Italy.
2
Centro di Biostatistica per l'epidemiologia clinica, Department of Health Sciences, University of Milano-Bicocca, Monza, 20900, Italy.
3
Department of Molecular Medicine, Sapienza University, Rome, 00161, Italy.
4
Department of Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
5
Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA.
6
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), San Raffaele Scientific Institute, Milan, 20132, Italy.
7
Vita Salute San Raffaele University, Milan, 20132, Italy.
8
Department of Pediatrics, University of Milano-Bicocca, Monza, 20900, Italy.
9
Dulbecco Telethon Institute, Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Monza, 20900, Italy. serafinim72@gmail.com.

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.

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