title: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.
abstract: The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.
authors.affiliation: Department of Pathology, Box 357470, Room D-514 HSB, University of Washington, Seattle, Washington 98195, USA. murry@u.washington.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
authors.forename: Mark H
authors.initials: MH
authors.lastname: Soonpaa
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Nakajima
authors.forename: Hisako O
authors.initials: HO
authors.lastname: Nakajima
authors.forename: Michael
authors.initials: M
authors.lastname: Rubart
authors.forename: Kishore B S
authors.initials: KB
authors.lastname: Pasumarthi
authors.forename: Jitka Ismail
authors.initials: JI
authors.lastname: Virag
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Bartelmez
authors.forename: Veronica
authors.initials: V
authors.lastname: Poppa
authors.forename: Gillian
authors.initials: G
authors.lastname: Bradford
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Dowell
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Field
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D012038:Regeneration; D019076:Transgenes / Q000235:genetics