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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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