title: Potential risks of bone marrow cell transplantation into infarcted hearts.
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.
authors.affiliation: Institute of Physiology I, University of Bonn, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Breitbach
authors.forename: Toktam
authors.initials: T
authors.lastname: Bostani
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
authors.forename: Oliver
authors.initials: O
authors.lastname: Dewald
authors.forename: Jens M
authors.initials: JM
authors.lastname: Nygren
authors.forename: Jochen W U
authors.initials: JW
authors.lastname: Fries
authors.forename: Klaus
authors.initials: K
authors.lastname: Tiemann
authors.forename: Heribert
authors.initials: H
authors.lastname: Bohlen
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Armin
authors.initials: A
authors.lastname: Welz
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
mesh_terms: 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
chemical_list: D049452:Green Fluorescent Proteins