Imperial College London
Alternate

DrMichaelThemis

Faculty of Natural Sciences, Department of Life Sciences (Silwood Park)

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)1895 267 252m.themis

 
 
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Location

 

Workspace 15Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chan:2007,
author = {Chan, J and Waddington, SN and O'Donoghue, K and Kurata, H and Guillot, PV and Gotherstrom, C and Themis, M and Morgan, JE and Fisk, NM},
journal = {Stem Cells},
pages = {875--884},
title = {Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17185606},
volume = {4},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Chan,J
AU  - Waddington,SN
AU  - O'Donoghue,K
AU  - Kurata,H
AU  - Guillot,PV
AU  - Gotherstrom,C
AU  - Themis,M
AU  - Morgan,JE
AU  - Fisk,NM
EP  - 884
PY  - 2007///
SP  - 875
TI  - Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse.
T2  - Stem Cells
UR  - http://www.ncbi.nlm.nih.gov/pubmed/17185606
VL  - 4
ER  -
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