Potential risks of bone marrow cell transplantation into infarcted hearts.
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.
Breitbach
Martin
M
Institute of Physiology I, University of Bonn, Bonn, Germany.
Bostani
Toktam
T
Roell
Wilhelm
W
Xia
Ying
Y
Dewald
Oliver
O
Nygren
Jens M
JM
Fries
Jochen W U
JW
Tiemann
Klaus
K
Bohlen
Heribert
H
Hescheler
Juergen
J
Welz
Armin
A
Bloch
Wilhelm
W
Jacobsen
Sten Eirik W
SE
Fleischmann
Bernd K
BK
D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D016896:Treatment Outcome
D049452:Green Fluorescent Proteins