Targeting of Lin-Sca+ hematopoietic stem cells with bispecific antibodies to injured myocardium
Targeting of Lin-Sca+ hematopoietic stem cells with bispecific antibodies to injured myocardium
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DOI：
10.1016/j.bcmd.2003.09.019
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发表时间：
2004-01-01
影响因子：
2.3
通讯作者：
Lee, RJ
中科院分区：
文献类型：
--
作者：
Lum, LG;Fok, H;Lee, RJ
双特异性抗体（BiAbs）被用于靶向T细胞或其他免疫细胞，以对抗抗原特异性肿瘤靶点。抗cd3激活T细胞（ATC）携带抗cd3 x抗Her2 BiAb （HER2Bi）已被用于靶向Her2/neu +乳腺癌和前列腺癌细胞。我们采用BiAb技术将干细胞靶向损伤心肌。由于心肌梗死可导致心脏死亡和残疾，受损心肌的快速修复和再生是迫切需要的。损伤心肌的修复需要有效地将干细胞归巢并将其转分化为心肌功能元件。我们使用一种BiAb结合小鼠干细胞上的c-kit和损伤心肌细胞上上调的VCAM-1粘附分子。为了测试小鼠的特异性结合和归巢，我们制作了anti-c-kit x anti-VCAM-1，将纯化的Lin - Sca+小鼠干细胞靶向损伤的心肌。通过结扎左前降动脉（LAD）造成梗死的小鼠直接注射武装干细胞或经荧光染料标记后经颈内静脉（IJ）注射FACS分选的骨髓Lin - Sca+干细胞。直接注射Lin - Sca+武装细胞后，梗死心肌中保留的Lin - Sca+武装细胞数量增加，注射IJ后，损伤心肌中保留的Lin - Sea+武装细胞数量增加。这些结果表明，用BiAb重靶向的干细胞可以直接注射并被损伤心肌保留，也可以靶向损伤心肌组织进行组织再生。(C) 2003 Elsevier Inc.版权所有。
Bispecific antibodies (BiAbs) are being used to target T cells or other immune cells to antigen-specific tumor targets. Anti-CD3 activated T cells (ATC) armed with anti-CD3 x anti-HER2 BiAb (HER2Bi) have been used to target Her2/neu + breast and prostate carcinoma cells. We adapted BiAb technology to target stem cells to injured myocardium. Since myocardial infarctions can lead to cardiac death and disability, rapid repair and rejuvenation of damaged myocardium is critically needed. Effective homing of stem cells and transdifferentiation of the stem cells into functional elements of the myocardium is needed for repair of damaged myocardium. We use a BiAb that binds c-kit on murine stem cells and VCAM-1 adhesion molecules up-regulated on injured myocardial cells. To test for specific binding and homing in a mouse, we produced anti-c-kit x anti-VCAM-1 to target purified Lin - Sca+ murine stem cells to the injured myocardium. Mice with infarcts created by ligation of the left anterior descending artery (LAD) were directly injected with armed stem cells or injected via the internal jugular vein (IJ) with FACS sorted Lin - Sca+ stem cells from bone marrow after fluorescent dye labeling. There were increased numbers of armed Lin - Sca+ cells retained in infracted myocardium after direct injection of armed Lin - Sca+ cells and increased numbers of Lin - Sea+ cells that were found in injured myocardium after IJ injection. These results suggest that stem cells retargeted with BiAb can be directly injected and retained by injured myocardium or targeted to injured myocardial tissues for tissue regeneration. (C) 2003 Elsevier Inc. All rights reserved.