Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19638-43. doi: 10.1073/pnas.1208384109. Epub 2012 Nov 12.
The environments that harbor hematopoietic stem and progenitor cells are critical to explore for a better understanding of hematopoiesis during health and disease. These compartments often are inaccessible for controlled and rapid experimentation, thus limiting studies to the evaluation of conventional cell culture and transgenic animal models. Here we describe the manufacture and image-guided monitoring of an engineered microenvironment with user-defined properties that recruits hematopoietic progenitors into the implant. Using intravital imaging and fluorescence molecular tomography, we show in real time that the cell homing and retention process is efficient and durable for short- and long-term engraftment studies. Our results indicate that bone marrow stromal cells, precoated on the implant, accelerate the formation of new sinusoidal blood vessels with vascular integrity at the microcapillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.
探索造血干细胞和祖细胞所处的环境对于更好地理解健康和疾病状态下的造血作用至关重要。这些环境通常难以进行受控和快速的实验,因此限制了对传统细胞培养和转基因动物模型的研究。在这里,我们描述了一种具有用户定义特性的工程微环境的制造和图像引导监测,该微环境可将造血祖细胞募集到植入物中。通过活体成像和荧光分子断层扫描,我们实时显示细胞归巢和保留过程在短期和长期植入研究中是高效且持久的。我们的结果表明,预先涂覆在植入物上的骨髓基质细胞可加速新的窦状血管形成,并且在微血管水平上保持血管完整性,从而增强了造血祖细胞向该部位的募集。这种可植入的构建体可用作研究造血作用的工具。