Targeting human CD34+ hematopoietic stem cells with anti-CD45 x anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction.
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 10(6) 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.
Zhao
Ting C
TC
Dept. of Pediatrics, Women and Infants Hospital, Providence, RI 02905, USA. Tzhao@wihri.org
Tseng
Andy
A
Yano
Naohiro
N
Tseng
Yitang
Y
Davol
Pamela A
PA
Lee
Randall J
RJ
Lum
Lawrence G
LG
Padbury
James F
JF
D000818:Animals; D018033:Antibodies, Bispecific; D018952:Antigens, CD34 / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000150:complications / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000276:immunology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D020257:Ventricular Remodeling
D018033:Antibodies, Bispecific; D018952:Antigens, CD34; D018994:Myosin Light Chains; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse