Human Umbilical Cord Blood–Derived CD133+ Cells Enhance Function and Repair of the Infarcted Myocardium

Author:

Leor Jonathan1,Guetta Esther2,Feinberg Micha S.1,Galski Hanan3,Bar Iris3,Holbova Radka1,Miller Liron1,Zarin Parvin1,Castel David1,Barbash Israel M.1,Nagler Arnon3

Affiliation:

1. Neufeld Cardiac Research Institute, Tel-Aviv University, Tel-Hashomer, Israel

2. Danek Gertner Institute of Human Genetics, Tel-Aviv University, Tel-Hashomer, Israel

3. Hematology Division and Cord Blood Bank, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel

Abstract

Abstract The use of adult stem cells for myocardial tissue repair might be limited in elderly and sick people because their cells are depleted and exhausted. The present study was conducted to explore the potential of human umbilical cord blood (UCB) CD133+ progenitor cells for myocardial tissue repair in a model of extensive myocardial infarction (MI). CD133+ progenitor cells were isolated from newborn UCB. Cells (1.2–2 × 106) or saline (control) was infused intravenously 7 days after permanent coronary artery ligation in athymic nude rats. Left ventricular (LV) function was assessed before and 1 month after infusion by echocardiography. Tracking of human cells was performed by fluorescent in situ hybridization for human X and Y chromosomes or by immunostaining for HLA-DR or HLA-ABC. One month after delivery, LV fractional shortening improved by 42 ± 17% in cell-treated hearts and decreased by 39 ± 10% in controls (p = .001). Anterior wall thickness decreased significantly in controls but not in treated hearts. Microscopic examination revealed that the UCB cells were able to migrate, colonize, and survive in the infarcted myocardium. Human cells were identified near vessel walls and LV cavity and were occasionally incorporated into endothelial cells in six of nine cell-treated animals but not in controls. Scar tissue from cell-treated animals was significantly populated with autologous myofibroblasts as indicated by colocalization of HLA-DR and α-smooth muscle actin staining. In conclusion, the present work suggests that, after MI, intravenous delivery of human UCB-derived CD133+ cells can produce functional recovery by preventing scar thinning and LV systolic dilatation.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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