Neonatal bone marrow transplantation in MPS IIIA Mice

Adeline A. Lau, N. Jannah Shamsani, Leanne K. Winner, Sofia Hassiotis, Barbara M. King, John J. Hopwood, Kim M. Hemsley

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

18 Citations (Scopus)


Patients with some neurological lysosomal storage disorders (LSD) exhibit improved clinical signs following bone marrow transplantation (BMT). The failure of mucopolysaccharidosis (MPS) type IIIA patients and adult mice with the condition to respond to this treatment may relate to factors such as impaired migration of donor-derived cells into the brain, insufficient enzyme production and/or secretion by the donor-derived microglial cells, or the age at which treatment is initiated. To explore these possibilities, we treated neonatal MPS IIIA mice with whole unfractionated bone marrow and observed that nucleated blood cell reconstitution occurred to a similar degree in MPS IIIA mice receiving green fluorescent protein (GFP)-expressing normal (treatment group) or MPS IIIA-GFP marrow (control group) and normal mice receiving normal-GFP marrow (control group). Further, similar distribution patterns of GFP+ normal or MPS IIIA donor–derived cells were observed throughout the MPS IIIA mouse brain. We demonstrate that N-sulfoglucosamine sulfohydrolase (SGSH), the enzyme deficient in MPS IIIA, is produced and secreted in a manner proportional to that of other lysosomal enzymes. However, despite this, overall brain SGSH activity was unchanged in MPS IIIA mice treated with normal marrow and the lysosomal storage burden in whole brain homogenates did not decrease, most likely due to donor-derived cells comprising <0.24% of total recipient brain cells in all groups. This suggests that the failure of MPS IIIA patients and mice to respond to BMT may occur as a result of insufficient donor-derived enzyme production and/or uptake by host brain cells.

Original languageEnglish
Title of host publicationJIMD Reports
Subtitle of host publicationCase and Research Reports, 2012/5
EditorsJ Zschocke, K Gibson, G Brown, E Morava, V Peters
Place of PublicationBerlin
Number of pages12
ISBN (Electronic)9783642334337
ISBN (Print)9783642334320
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Publication series

NameJIMD Reports
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312


  • Bone marrow transplantation
  • Donor cell
  • Green fluorescent protein
  • Heparan sulfate
  • Neutrophil elastase


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