Au Patrick, Daheron Laurence M, Duda Dan G, Cohen Kenneth S, Tyrrell James A, Lanning Ryan M, Fukumura Dai, Scadden David T, Jain Rakesh K
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Blood. 2008 Feb 1;111(3):1302-5. doi: 10.1182/blood-2007-06-094318. Epub 2007 Nov 9.
Tissue engineering requires formation of a de novo stable vascular network. Because of their ability to proliferate, differentiate into endothelial cells, and form new vessels, blood-derived endothelial progenitor cells (EPCs) are attractive source of cells for use in engineering blood vessels. However, the durability and function of EPC-derived vessels implanted in vivo are unclear. To this end, we directly compared formation and functions of tissue-engineered blood vessels generated by peripheral blood- and umbilical cord blood-derived EPCs in a model of in vivo vasculogenesis. We found that adult peripheral blood EPCs form blood vessels that are unstable and regress within 3 weeks. In contrast, umbilical cord blood EPCs form normal-functioning blood vessels that last for more than 4 months. These vessels exhibit normal blood flow, perm-selectivity to macromolecules, and induction of leukocyte-endothelial interactions in response to cytokine activation similar to normal vessels. Thus, umbilical cord blood EPCs hold great therapeutic potential, and their use should be pursued for vascular engineering.
组织工程需要构建一个全新的稳定血管网络。血液来源的内皮祖细胞(EPCs)具有增殖、分化为内皮细胞并形成新血管的能力,因此是用于血管工程的极具吸引力的细胞来源。然而,体内植入的EPC来源血管的耐久性和功能尚不清楚。为此,我们在体内血管生成模型中直接比较了外周血和脐带血来源的EPCs所生成的组织工程血管的形成和功能。我们发现,成体外周血EPCs形成的血管不稳定,在3周内就会退化。相比之下,脐带血EPCs形成的血管功能正常,可持续4个多月。这些血管表现出正常的血流、对大分子的通透选择性,以及在细胞因子激活后诱导白细胞与内皮细胞相互作用,类似于正常血管。因此,脐带血EPCs具有巨大的治疗潜力,应将其用于血管工程。