HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 104/6/1793    most recent 01109.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhao, T. C. Articles by Padbury, J. F. Search for Related Content PubMed PubMed Citation Articles by Zhao, T. C. Articles by Padbury, J. F.

Targeting human CD34⁺ hematopoietic stem cells with anti-CD45 x anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction

¹Department of Pediatrics, Women and Infants Hospital, The Warren Alpert Medical School at Brown University, Providence, Rhode Island; ²Department of Research, Roger Williams Medical Center, Providence, Rhode Island; ³University of California-San Francisco, San Francisco, California; and ⁴Karmanos Cancer Institute and Departments of Medicine and Immunology and Microbiology, Wayne State University, Detroit, Michigan

Submitted 16 October 2007 ; accepted in final form 12 February 2008

We have previously shown that targeting human CD34⁺ hematopoietic stem cells (HSC) with a bispecific antibody (BiAb) directed against myosin light chain (MLC) increases delivery of cells to the injured hearts and improves cardiac performance in the nude rat. In this study, we have sought to validate our previous observations and to perform more detailed determination of ventricular function in immunocompetent mice with myocardial infarction (MI) that were treated with armed CD34⁺ HSC. We examined whether armed CD34⁺ HSC would target the injured heart following MI and restore ventricular function in vitro. MI was created by ligation of the left anterior descending artery. After 48 h, adult ICR mice received either 0.5 x 10⁶ human CD34⁺ HSC armed with anti-CD45 x anti-MLC BiAb or an equal volume of medium through a single tail vein injection. Two weeks after stem cell administration, ventricular function of hearts from mice receiving armed CD34⁺ HSC was significantly greater compared with the same parameters from control mice. Immunohistochemistry confirmed the accumulation of CD34⁺ HSC in MI hearts infused with stem cells. Angiogenesis was significantly enhanced in CD34⁺ HSC-treated heart as determined by vascular density per area. Furthermore, histopathological examination revealed that the retained cardiac function observed in CD34⁺ HSC-treated mice was associated with decreased ventricular fibrosis. These results suggest that peripheral administration of armed CD34⁺ HSC results in localization of CD34⁺ HSC to injured myocardium and restores myocardial function.

CD34⁺ hematopoietic stem cell; bispecific antibody; mouse; myocardium

This article has been cited by other articles:

				K. D. Boudoulas and A. K. Hatzopoulos Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease Dis. Model. Mech., July 1, 2009; 2(7-8): 344 - 358. [Abstract] [Full Text] [PDF]