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.

Azario, I., Pievani, A., Del Priore, F., Antolini, L., Santi, L., Corsi, A., et al. (2017). Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I. SCIENTIFIC REPORTS, 7(1) [10.1038/s41598-017-09958-9].

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

Azario, I;Pievani, A;Antolini, L;SANTI, LUDOVICA;Valsecchi, MG;Biondi, A;Serafini, M
2017

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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Articolo in rivista - Articolo scientifico
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Multidisciplinary
English
Azario, I., Pievani, A., Del Priore, F., Antolini, L., Santi, L., Corsi, A., et al. (2017). Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I. SCIENTIFIC REPORTS, 7(1) [10.1038/s41598-017-09958-9].
Azario, I; Pievani, A; Del Priore, F; Antolini, L; Santi, L; Corsi, A; Cardinale, L; Sawamoto, K; Kubaski, F; Gentner, B; Bernardo, M; Valsecchi, M; Riminucci, M; Tomatsu, S; Aiuti, A; Biondi, A; Serafini, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/182421
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