Hasson Eilat, Gallula Jeniffer, Shimoni Yael, Grad-Itach Etty, Marikovsky Moshe, Mitrani Eduardo
Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Vasc Res. 2006;43(2):139-48. doi: 10.1159/000090943. Epub 2006 Jan 11.
We have recently reported an alternative cell therapy approach to induce angiogenesis. The approach is based on small organ fragments--micro-organs (MOs)--whose geometry allows preservation of the natural epithelial/mesenchymal interactions and ensures appropriate diffusion of nutrients and gases to all cells. We have shown that lung-derived MOs, when implanted into hosts, transcribe a wide spectrum array of angiogenic factors and can induce an angiogenic response that can rescue experimentally induced ischemic regions in mice. From a clinical perspective, skin-derived MOs are particularly appealing as they could readily be obtained from a skin biopsy taken from the same target patient. In the present work we have investigated the angiogenesis-inducing capacity of rabbit and human skin-derived micro-organs in vitro and in vivo. Rabbit skin MOs were implanted into homologous adult rabbits and human skin MOs were encapsulated and implanted into xenogenic mice. Skin-derived MOs, as lung-derived MOs, were found to secrete a whole array of angiogenic factors and to induce a powerful angiogenic response when implanted back into animals. We believe the approach presented suggests a novel, efficacious and simple approach for therapeutic angiogenesis.
我们最近报道了一种诱导血管生成的替代性细胞治疗方法。该方法基于小器官碎片——微型器官(MOs),其几何结构能够保留天然的上皮/间充质相互作用,并确保营养物质和气体向所有细胞的适当扩散。我们已经表明,源自肺的MOs植入宿主后,会转录一系列广泛的血管生成因子,并能诱导血管生成反应,从而挽救小鼠实验性诱导的缺血区域。从临床角度来看,源自皮肤的MOs特别有吸引力,因为它们可以很容易地从同一目标患者的皮肤活检中获得。在本研究中,我们研究了兔和人皮肤来源的微型器官在体外和体内诱导血管生成的能力。将兔皮肤MOs植入同种成年兔体内,将人皮肤MOs封装后植入异种小鼠体内。结果发现,与源自肺的MOs一样,源自皮肤的MOs分泌一系列血管生成因子,并在植入动物体内后诱导强烈的血管生成反应。我们认为所提出的方法为治疗性血管生成提供了一种新颖、有效且简单的方法。