Melero-Martin Juan M, De Obaldia Maria E, Kang Soo-Young, Khan Zia A, Yuan Lei, Oettgen Peter, Bischoff Joyce
Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Circ Res. 2008 Jul 18;103(2):194-202. doi: 10.1161/CIRCRESAHA.108.178590. Epub 2008 Jun 12.
The success of therapeutic vascularization and tissue engineering will rely on our ability to create vascular networks using human cells that can be obtained readily, can be expanded safely ex vivo, and can produce robust vasculogenic activity in vivo. Here we describe the formation of functional microvascular beds in immunodeficient mice by coimplantation of human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow. Evaluation of implants after 1 week revealed an extensive network of human blood vessels containing erythrocytes, indicating the rapid formation of functional anastomoses within the host vasculature. The implanted endothelial progenitor cells were restricted to the luminal aspect of the vessels; mesenchymal progenitor cells were adjacent to lumens, confirming their role as perivascular cells. Importantly, the engineered vascular networks remained patent at 4 weeks in vivo. This rapid formation of long-lasting microvascular networks by postnatal progenitor cells obtained from noninvasive sources constitutes an important step forward in the development of clinical strategies for tissue vascularization.
治疗性血管生成和组织工程的成功将取决于我们利用人类细胞构建血管网络的能力,这些细胞应易于获取、能在体外安全扩增,并能在体内产生强大的血管生成活性。在此,我们描述了通过共植入从血液和骨髓中分离出的人类内皮祖细胞和间充质祖细胞,在免疫缺陷小鼠体内形成功能性微血管床的过程。对植入物1周后的评估显示,存在一个包含红细胞的广泛人类血管网络,这表明在宿主脉管系统内迅速形成了功能性吻合。植入的内皮祖细胞局限于血管的管腔面;间充质祖细胞与管腔相邻,证实了它们作为血管周细胞的作用。重要的是,工程化血管网络在体内4周时仍保持通畅。从非侵入性来源获得的出生后祖细胞快速形成持久的微血管网络,这是组织血管化临床策略发展中的重要一步。