Purchase this article with an account.
Vivien Coulson-Thomas, Bruce Caterson, Chia-Yang Liu, Winston Kao; Transpalntation of umbilical mesenchymal stem cells cures the corneal defects of Mucopolysaccharidosis VII mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1009.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Mucopolysaccharidoses (MPS) are a family of related disorders caused by a mutation in one of the lysosomal exoglycosidases required for the sequential degradation of glycosaminoglycans (GAGs). MPS are progressive disorders in which GAGs and their metabolic derivatives accumulate in lysosomes compromising cellular activity and ultimately leading to cell death. MPS VII, Sly syndrome, caused by a mutation in β-glucuronidase, manifests as hepatomegaly, skeletal dysplasia, short stature, corneal clouding and developmental delay, due to the accumulation of heparan sulfate (HS), dermatan sulfate and chondroitin 4,6-sulfate (CS). Current treatment regimens for MPS are not effective for treating corneal clouding and mental development.
We hypothesized that umbilical mesenchymal stem cells (UMSC) transplanted into the corneal stroma can participate in the catabolism of GAGs, thus providing a means of cell therapy for MPS. For such, human UMSC were intrastromally transplanted into corneas of 1, 2 and 3 month-old MPS VII mice.
UMSC transplantation restored the dendritic and hexagonal morphology of host keratocytes and endothelial cells, respectively, and in vivo confocal microscopy (HRTII) revealed reduced corneal haze. Immunohistochemistry using antibodies against HS and CS chains, as well as, LAMP2 revealed a decrease in GAG content and both lysosomal number and size in the treated corneas to levels similar to that of littermate controls. Labeling UMSC intracellular compartments prior to transplantation revealed the distribution of UMSC exosomes throughout the corneal stroma and endothelium. An in vitro co-culture assay between skin fibroblasts isolated from MPSVII mice and UMSC labeled with LysoSensor demonstrated that neutral exosomes released by the UMSC are up taken by the fibroblasts and proceed to fuse with the acidic lysosomes.
Therefore, transplanted UMSC participate in extracellular GAG turnover and aid host keratocytes to metabolize accumulated GAG, suggesting that UMSC could be a good alternative for treating corneal defects associated with MPS and other congenital metabolic disorders. Moreover, given the simplicity of the treatment, we suggest it as prophylactic treatment upon diagnosis in order to avoid the development of corneal clouding.
This PDF is available to Subscribers Only