Abstract 17245: The Intelligent Modulation of Stem Cell Niches by the Implantation of Collagen Binding Domain Laminin-511 Conjugating Collagen Sheet Repair the Damaged Myocardium by Enhancing Stem Cell Homing
Background: Recently it has become increasingly evident that the extracellular matrix (ECM), particularly basement membrane components such as laminins (LMs), plays important roles for differentiation and self-renewal of stem cells. New therapeutic strategy targeted ECM may open new era for the treatment of heart failure. In this study, we focused on the main component of basement membrane LMs and hypothesized that these ECM proteins may impact on regeneration process by modulation of stem cell activity in vitro and vivo.
Methods and Results: Immunostains revealed that LM511 and LM221 were main ECM components of epicardium where stem cells were abundant. In vitro study, we examined the adhesive and proliferation activities to LM511 and LM221 of MSCs which express some integrins on cell surface. Although MSCs showed strong adhesive and proliferate activities on LM511, it showed weak adhesive and proliferate activities on LM221. To examine the therapeutic effect of the LMs, we produced recombinant LMs fused with the collagen binding domain (CBD) of fibronectin to immobilize them on collagen sheets and transplanted sheets with or without CBD-LM511 and CBD-LM221 in rat acute myocardial infarction model. Four week later, histological examination revealed that the number of ILB4 (endothelial cell marker) positive cells were significantly higher in CBD-LM511 group compared with CBD-LM221 group (CBD-LM511: 1289±172 cells/mm2, CBD-LM221: 925±142 cells/mm2, control: 768±141 cells/mm2; p<0.05). Moreover, the number of ILB4 positive cells which expressed both PDGFR and CD90 on cell membrane was significantly higher in CBD-LM511 group compared with CBD-LM221 group and the control (CBD-LM511: 531±322 cells/mm2, CBD-LM221: 240±126 cells/mm2, control: 160±97 cells/mm2 ; p<0.05 ), suggesting that LM511 enhance the recruitment and attachment of MSCs in the implanted site. In addition, there were many large vessels in CBD-LM511 group. Real time PCR analysis revealed that SDF-1, PGF and FGF2 were higher in CBD-LM511 group.
Conclusion: The transplantation of CBD-LM511 conjugating collagen sheet may contribute to homing of MSCs to implanted site by modulating stem cell niches in epicardium, leading to therapeutic impact of angiogenesis in rat ischemic heart.
- © 2013 by American Heart Association, Inc.