Myocardial infarction can lead to death and disability with a 5-year mortality rate of 50% in patients with congestive heart failure (1,2). Currently, heart transplantation is the only successful treatment for end-stage heart failure; however, the ability to provide this treatment is limited by the availability of donor hearts (3,4). Therefore, alternative therapies are needed to treat end-stage heart failure. Recently, significant advances in cellular transplantation has gained enthusiasm as an alternative treatment for myocardial repair. The delivery of bone marrow-derived stem cells via direct intramyocardial injection or intracoronary injection has been shown to improve myocardial left ventricular (LV) function following a myocardial infarction. Our laboratories have recently adapted a technology used in the cancer field to develop an approach to target stem cells to injury antigens delivered peripherally. Preliminary data demonstrates that stem cells derived from human peripheral blood can be bispecific antibody (BiMab) targeted to injured myocardium when injected intravenously in a rodent model of ischemia-reperfusion induced myocardial infarction. This less invasive approach has obvious advantages as a potential systemic delivery system and as a tool to investigate stem cell differentiation. ? ? 1.3 Hypothesis: ? 1. BiMab targeting of stem cells (SC) results in greater myocardial retention of SC than either direct intramyocardial or intravenous administration of SC. 2. The microenvironment of the ischemic myocardium influences SC differentiation, angiogenesis and ventricular remodeling. ? ? 1.
4 Specific aims : ? Specific Aim 1. To assess the biodistribution of BiMab targeted SC to different target antigens expressed in ischemic myocardium. ? Specific aim 2: To test the hypothesis that the microenvironment influences SC differentiation, angiogenesis and LV remodeling. ? ? ?
| Yu, Jiashing; Wu, Yuan-Kun; Gu, Yiping et al. (2015) Immuno-modification of enhancing stem cells targeting for myocardial repair. J Cell Mol Med 19:1483-91 |
| Mihardja, Shirley S; Gonzales, Jose A; Gao, Dongwei et al. (2013) The effect of a peptide-modified thermo-reversible methylcellulose on wound healing and LV function in a chronic myocardial infarction rodent model. Biomaterials 34:8869-77 |
| Mihardja, Shirley S; Gao, Dongwei; Sievers, Richard E et al. (2010) Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction. PLoS One 5:e10384 |
| Mihardja, Shirley S; Sievers, Richard E; Lee, Randall J (2008) The effect of polypyrrole on arteriogenesis in an acute rat infarct model. Biomaterials 29:4205-10 |
