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Translational and Clinical Research
Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation†‡§
Article first published online: 18 JUN 2012
DOI: 10.1002/stem.1118
Copyright © 2012 AlphaMed Press
Additional Information
How to Cite
von Bahr, L., Batsis, I., Moll, G., Hägg, M., Szakos, A., Sundberg, B., Uzunel, M., Ringden, O. and Le Blanc, K. (2012), Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation. STEM CELLS, 30: 1575–1578. doi: 10.1002/stem.1118
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Author contributions: L.v.B.: collection and assembly of data, data analysis and interpretation, manuscript writing, and revised and approved of the manuscript; I.B.: conception and design, collection and assembly of data, and revised and approved of the manuscript; G.M.: data analysis and interpretation and revised and approved of the manuscript; M.H.: collected data and revised and approved of the manuscript; A.S.: provision of study material, collection of data, and revised and approved of the manuscript; B.S.: collection and assembly of data and revised and approved of the manuscript; M.U.: collection of data, data analysis and interpretation, and revised and approved of the manuscript; O.R.: concept and design and revised and approved of the manuscript; K.L.B.: concept and design, data analysis and interpretation, manuscript writing, revised and approved of the manuscript.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLSEXPRESS May 2, 2012.
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Publication History
- Issue published online: 18 JUN 2012
- Article first published online: 18 JUN 2012
- Accepted manuscript online: 2 MAY 2012 08:52AM EST
- Manuscript Accepted: 16 MAR 2012
- Manuscript Received: 24 JAN 2012
Funded by
- Swedish Cancer Foundation. Grant Number: 110315
- Children's Cancer Foundation. Grant Number: 08/071
- Swedish Research Council. Grant Number: K2011-??X-20742-04-6
- Tobias Foundation, VINNOVA. Grant Number: 2010-00501
- Stockholm City Council (ALF). Grant Number: 20110152
- Cancer Society in Stockholm
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- Cited By
Keywords:
- Mesenchymal stromal cells;
- Cell transplantation;
- Humans;
- Polymerase chain reaction;
- Graft survival
Abstract
Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a “hit and run” mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy. STEM CELLS2012;30:1575–1578

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