Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/62914
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Type: Journal article
Title: Embryonic stem cell-derived glial precursors as a vehicle for sulfamidase production in the MPS-IIIA mouse brain
Author: Robinson, A.
Zhao, G.
Rathjen, J.
Rathjen, P.
Hutchinson, R.
Eyre, H.
Hemsley, K.
Hopwood, J.
Citation: Cell Transplantation, 2010; 19(8):985-998
Publisher: Cognizant Communication Corp
Issue Date: 2010
ISSN: 0963-6897
1555-3892
Statement of
Responsibility: 
Aaron J. Robinson, Guoying Zhao, Joy Rathjen, Peter D. Rathjen, Rhonda G. Hutchinson, Helen J. Eyre, Kim M. Hemsley, and John J. Hopwood
Abstract: Pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, have generated much excitement about their prospects for use in cell transplantation therapies. This is largely attributable to their virtually unlimited growth potential, their ability to be precisely genetically altered in culture, and their utility for forming differentiated cell populations with potential clinical applications. Lysosomal storage diseases such as Sanfilippo syndrome (MPS-IIIA) represent ideal candidate diseases for the evaluation of cell therapies in the central nervous system (CNS). These diseases exhibit widespread pathology yet result from a single gene deficiency, in the case of Sanfilippo syndrome the lysosomal enzyme sulfamidase. The aim of this study was to investigate mouse embryonic stem (ES) cell-derived glial precursor cells as a vehicle for sulfamidase delivery in the MPS-IIIA mouse brain. In this study we have created a mouse ES cell line genetically modified to stably express and secrete high levels of human sulfamidase and a protocol for the in vitro derivation of large numbers glial precursors from ES cells. Differentiation of sulfamidase-expressing ES cells resulted in cell populations with sustained secretion of high levels of sulfamidase, comprised primarily of glial precursor cells with minor contaminants of other neural cell phenotypes but not residual pluripotent cells. CNS implantation studies demonstrated that ES cell-derived glial precursor cells formed using this differentiation method were able to engraft and survive for at least 12 weeks following implantation. The percentage of engraftment was quantified in different regions of the brain in 2-, 4-, and 8-week-old normal and MPS-IIIA mice. No teratomas were observed in any of the cell-transplanted animals. The results of this study support the further investigation of sulfamidase-expressing glial precursor cells as a vehicle for delivery of deficient enzyme into the CNS of MPS-IIIA mice.
Keywords: Cell therapy; Glial precursor cell; Embryonic stem cell; Lysosomal storage disease; Central nervous system
Rights: Copyright © 2010 Cognizant Comm. Corp.
RMID: 0020101401
DOI: 10.3727/096368910X498944
Appears in Collections:Paediatrics publications

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