Chavakis Emmanouil, Urbich Carmen, Dimmeler Stefanie
Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
J Mol Cell Cardiol. 2008 Oct;45(4):514-22. doi: 10.1016/j.yjmcc.2008.01.004. Epub 2008 Jan 18.
Cell therapy is a promising therapeutic option for treating patients with ischemic diseases. The efficiency of cell therapy to augment recovery after ischemia depends on the sufficient recruitment of applied cells to the target tissue. Using in vivo imaging techniques the extent of homing was shown to be rather low in most experimental and clinical studies. The elucidation of the molecular mechanisms of homing of different progenitor cell subpopulation to sites of injury is essential for the development of new specific therapeutic strategies, in order to improve the efficacy of cell-based therapies. Homing to sites of active neovascularization is a complex process depending on a timely and spatially orchestrated interplay between chemokines (e.g. SDF-1), chemokine receptors, intracellular signaling, adhesion molecules (selectins and integrins) and proteases. The review will focus on the mechanisms underlying homing of adult bone marrow-derived hematopoietic cells, mesenchymal stem cells, and vasculogenic circulating cells and discuss strategies how to optimize cell engraftment.
细胞疗法是治疗缺血性疾病患者的一种有前景的治疗选择。细胞疗法增强缺血后恢复的效率取决于所应用的细胞向靶组织的充分募集。在大多数实验和临床研究中,使用体内成像技术显示归巢程度相当低。阐明不同祖细胞亚群归巢至损伤部位的分子机制对于开发新的特异性治疗策略至关重要,以便提高基于细胞的疗法的疗效。归巢至活跃血管生成部位是一个复杂的过程,这取决于趋化因子(如SDF-1)、趋化因子受体、细胞内信号传导、黏附分子(选择素和整合素)和蛋白酶之间及时且空间协调的相互作用。本综述将聚焦于成年骨髓来源的造血细胞、间充质干细胞和血管生成循环细胞归巢的潜在机制,并讨论如何优化细胞植入的策略。