title: Minimal engraftment of human CD34+ cells mobilized from healthy donors in the infarcted heart of athymic nude rats.
abstract: Cell-based regenerative therapy may be useful for treatment of acute myocardial infarction (AMI). Animal xenograft models are ideally suited for preclinical studies evaluating prospective treatment regimes, identifying candidate human cell populations, and gaining mechanistic insight. Here we address whether the athymic nude rat is suitable as a xenograft model for the study of human CD34+ mobilized peripheral blood stem cells (M-PBSCs) in the repair of AMI. We injected human donor cells into the infarct border of athymic nude rats with surgically induced AMI and evaluated engraftment and functional improvement. We found no human engraftment by immunofluorescence staining at 14 days after transplantation or functional improvement at days 2 and 14 compared to controls. The lack of long-term human engraftment was furthermore confirmed in a time series study analyzing animals at 0, 24, 48, 72, and 96 h after transplantation. Although we found fluorescent microbeads coinjected with human CD34+ M-PBSCs at all time points, the number of donor cells rapidly declined and became undetectable at 96 h. CD34+ M-PBSCs from the same donor used to treat athymic nude rat hearts engrafted the bone marrow of nonobese diabetic/severe combined immunodeficient mice 8-10 weeks after transplantation. In conclusion, human CD34+ M-PBSCs with confirmed hematopoietic engraftment potential rapidly disappeared from the site of injury following intramyocardial transplantation in the athymic nude rat AMI model.
authors.affiliation: Institute of Clinical Medicine, Arhus University Hospital, Arhus, Denmark.
authors.forename: Claus S
authors.initials: CS
authors.lastname: Sondergaard
authors.forename: Jesper
authors.initials: J
authors.lastname: Bonde
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: Jan M
authors.initials: JM
authors.lastname: Nielsen
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zachar
authors.forename: Mette
authors.initials: M
authors.lastname: Holm
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.forename: Lene
authors.initials: L
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D005434:Flow Cytometry; D005453:Fluorescence; D006262:Health; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D011923:Rats, Nude; D013997:Time Factors; D014019:Tissue Donors; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D018952:Antigens, CD34; D017493:Leukocyte Common Antigens