TISSUE IMAGING IN CELL BIOLOGY

我们已经开始研究厚组织中细胞行为的各个方面： 细胞运动、细胞增殖和细胞融合。这些 多细胞生物体中的基本生物学过程 多年来，人们一直在研究从组织中分离的细胞。 然而，在体内，所有这些事件都受到情结的影响， 活体组织的异质微环境。我们已经开发出 一种研究细胞行为的新方法，包括长期 培养未受干扰的小鼠和人类组织块并 激光共聚焦显微镜观察这些组织内的单个细胞。 这些新开发的技术已被用于研究肿瘤 侵犯正常组织。我们已经证明， 肿瘤细胞受其周围正常环境的影响很大 组织。不均匀的组织微环境导致 肿瘤细胞的非均匀侵袭，产生细胞的“流” 一个接一个的。这个系统提供了一个机会 直接观察肿瘤的侵袭，并增加了 研究各种药物对这一过程的影响。 在活体内也进行了厚组织成像以测试 感染性休克的机制。大鼠的阻力小动脉 对提睾肌进行成像，对儿茶酚胺的反应是 量过了。与脓毒症动物相比，败血症动物的血管收缩功能受损 到控制程序。抑制一氧化氮合酶逆转了这一趋势 反应迟钝。通过成像实际负责的血管 对于脓毒症中TPR的下降，病理生理学假说 因此可以直接进行测试，而不是从模型中推断 大动脉等组织。

We have begun to study aspects of cell behavior in thick tissues: cell locomotion, cell proliferation and cell fusion. These fundamental biological processes in multicellular organisms have for many years been studied on cells isolated from tissue. However, in vivo, all these events are influenced by the complex, heterogeneous microenvironment of living tissue. We have developed a new approach to studying cell behavior which includes long-term culturing of blocks of unperturbed mouse and human tissues and confocal laser microscopy of individual cells inside these tissues. These newly developed techniques have been used to study tumor invasion of normal tissue. We have shown that the behavior of tumor cells is significantly affected by their surrounding normal tissue. An inhomogeneous tissue microenvironment results in nonuniform invasion of tumor cells which produce "streams" of cells following each other. This system provides an opportunity for direct observation of tumor invasion and raises the possibility of studying the effects of various drugs on this process. Thick tissue imaging was also implemented in vivo to test the mechanism of septic shock. Resistance arterioles of the rat cremaster muscle were imaged and the response to catecholamines was measured. Septic animals showed impaired vasoconstriction compared to controls. Inhibiting nitric oxide synthase reversed this hyporesponsiveness. By imaging the vessels actually responsible for the decrease of TPR seen in sepsis, pathophysiologic hypotheses can thus be directly tested rather than extrapolated from model tissues such as aorta.