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Potential risks of bone marrow cell transplantation into infarcted hearts

Breitbach, Martin; Bostani, Toktam; Roell, Wilhelm; Xia, Ying; Dewald, Oliver; Nygren, Jens LU ; Fries, Jochen W. U.; Tiemann, Klaus; Bohlen, Heribert and Hescheler, Juergen, et al. (2007) In Blood 110(4). p.1362-1369
Abstract
Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained... (More)
Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors (0 of 5, 0.0%), fibroblasts (0 of 5, 0.0%), vehicle only (0 of 30, 0.0%), or cytokine-induced mobilization of BM cells (0 of 35, 0.0%). We conclude that the developmental fate of BM-derived cells is not restricted by the surrounding tissue after myocardial infarction and that the MSC fraction underlies the extended bone formation in the infarcted myocardium. These findings seriously question the biologic basis and clinical safety of using whole BM and in particular MSCs to treat nonhematopoietic disorders. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
110
issue
4
pages
1362 - 1369
publisher
American Society of Hematology
external identifiers
  • wos:000248655300045
  • scopus:34548044258
ISSN
1528-0020
DOI
10.1182/blood-2006-12-063412
language
English
LU publication?
yes
id
c2658a25-206a-4ce6-9375-344e5cf47bcd (old id 656696)
date added to LUP
2007-12-05 12:42:46
date last changed
2017-11-19 03:34:14
@article{c2658a25-206a-4ce6-9375-344e5cf47bcd,
  abstract     = {Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors (0 of 5, 0.0%), fibroblasts (0 of 5, 0.0%), vehicle only (0 of 30, 0.0%), or cytokine-induced mobilization of BM cells (0 of 35, 0.0%). We conclude that the developmental fate of BM-derived cells is not restricted by the surrounding tissue after myocardial infarction and that the MSC fraction underlies the extended bone formation in the infarcted myocardium. These findings seriously question the biologic basis and clinical safety of using whole BM and in particular MSCs to treat nonhematopoietic disorders.},
  author       = {Breitbach, Martin and Bostani, Toktam and Roell, Wilhelm and Xia, Ying and Dewald, Oliver and Nygren, Jens and Fries, Jochen W. U. and Tiemann, Klaus and Bohlen, Heribert and Hescheler, Juergen and Welz, Armin and Bloch, Wilhelm and Jacobsen, Sten Eirik W and Fleischmann, Bernd K.},
  issn         = {1528-0020},
  language     = {eng},
  number       = {4},
  pages        = {1362--1369},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Potential risks of bone marrow cell transplantation into infarcted hearts},
  url          = {http://dx.doi.org/10.1182/blood-2006-12-063412},
  volume       = {110},
  year         = {2007},
}