Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse

Chan, Jerry, Waddington, Simon N., O'Donoghue, Keelin, Kurata, Hitoshi, Guillot, Pascale V., Gotherstrom, Cecilia, Themis, Michael, Morgan, Jennifer E. and Fisk, Nicholas M. (2007) Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse. Stem Cells, 25 4: 875-884.


Author Chan, Jerry
Waddington, Simon N.
O'Donoghue, Keelin
Kurata, Hitoshi
Guillot, Pascale V.
Gotherstrom, Cecilia
Themis, Michael
Morgan, Jennifer E.
Fisk, Nicholas M.
Title Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse
Formatted title Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2007-04
Year available 2006
Sub-type Article (original research)
DOI 10.1634/stemcells.2006-0694
Volume 25
Issue 4
Start page 875
End page 884
Total pages 10
Editor Donald G. Phinney
Miodrag Stojković
Place of publication Durham, NC, U.S.
Publisher Wiley-Blackwell and AlphaMed Press
Language eng
Subject 111401 Foetal Development and Medicine
111402 Obstetrics and Gynaecology
1114 Paediatrics and Reproductive Medicine
Formatted abstract Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, we investigated a fetal-to-fetal transplantation strategy. We investigated intramuscular, intravascular, and intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into embryonic day (E) 14-16 MF1 mice to determine the most appropriate route for systemic delivery. Intramuscular injections resulted in local engraftment, whereas both intraperitoneal and intravascular delivery led to systemic spread. However, intravascular delivery led to unexpected demise of transplanted mice. Transplantation of hfMSCs into E14-16 mdx mice resulted in widespread long-term engraftment (19 weeks) in multiple organs, with a predilection for muscle compared with nonmuscle tissues (0.71% vs. 0.15%, p < .01), and evidence of myogenic differentiation of hfMSCs in skeletal and myocardial muscle. This is the first report of intrauterine transplantation of ontologically relevant hfMSCs into fully immunocompetent dystrophic fetal mice, with systemic spread across endothelial barriers leading to widespread long-term engraftment in multiple organ compartments. Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology. Disclosure of potential conflicts of interest is found at the end of this article.
Copyright © 2010 AlphaMed Press.

Keyword Duchenne muscular dystrophy
Dystrophin
Human fetal mesenchymal stem cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 52 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 62 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 50 Abstract Views  -  Detailed Statistics
Created: Fri, 20 Mar 2009, 17:06:23 EST by Mary-Anne Marrington on behalf of Faculty Of Health Sciences