Engineering tissues and organs in vivo from stem cells

组织工程是医学研究的一个令人兴奋的新领域。我们开发了一种独特的组织工程动物模型，新组织自发地从封闭在塑料腔室中的血管环表面发芽。这样产生的组织有自己的血液供应。通过添加培养的细胞或改变腔室的环境，我们已经能够生长新的特定组织，如脂肪和肌肉。这项技术有可能产生备用的身体部位，以取代丢失或磨损的器官和组织。我们最近在小鼠中复制了这种模型，以便能够筛选一系列小鼠和人类干细胞。这些细胞有能力改变（即分化）成许多不同类型的细胞，这取决于它们如何被刺激。在本项目的第1部分中，我们将在小鼠室中确定这些干细胞的生长特性和存活率。将在每个腹股沟皮下植入一个包封流动血管的腔室。在一个腔室中，我们将在生长培养基中注射荧光标记的干细胞，并单独在另一种生长培养基中注射。将在第1、2和4周时分析组织。在第2部分中，我们将注射从几种不同组织中获得的各种Rosa26标记的小鼠干细胞。通过天然存在的生长和分化因子的帮助，它们将分化成几种不同组织之一，包括脂肪、软骨、骨、神经组织、血管、肝等，其将通过组织学和细胞培养来鉴定。在一个实验中，我们将对注入腔室的细胞进行遗传改变，使它们只产生骨骼肌。在第3部分中，我们将通过将人类干细胞注射到小鼠的相同组织工程室中来生长新的人体组织，这些小鼠将耐受来自其他哺乳动物的细胞（这些被称为SCID小鼠）。新方法的成功将是生产新的人体组织来修复特定缺陷的先驱。

Tissue engineering is an exciting new area of medical research. We have developed a unique animal model of tissue engineering where new tissue spontaneously sprouts from the surface of a vascular loop enclosed inside a plastic chamber. The tissue thus created has its own blood supply. By adding cultured cells or altering the environment of the chamber we have been able to grow new specific tissues such as fat and muscle. This technology potentially allows the generation of spare body parts to replace lost or worn out organs and tissues. We have recently reproduced this model in the mouse to be able to screen a range of mouse and human stem cells. These cells have the ability to change (i.e. differentiate) into many different types of cell depending on how they are stimulated. In Part 1 of this project we will determine in the mouse chamber the growth characteristics and survival rates of these stem cells. A chamber encapsulating a flowing blood vessel will be implanted subcutaneously in each groin. In one chamber we will inject fluorescently labelled stem cells in a growth medium and in the other growth medium alone. Tissue will be analysed at 1, 2 and 4 weeks. In Part 2 we will inject a variety of Rosa26 labelled mouse stem cells obtained from several different tissues. Through the aid of naturally occurring growth and differentiation factors they will differentiate into one of several different tissues including fat, cartilage, bone, neural tissue, blood vessels, liver, etc, which will be identified by histology and cell culture. In one experiment we will genetically alter cells injected into the chamber so that they produce only skeletal muscle. In Part 3 we will grow new human tissues by injecting human stem cells into the same tissue engineering chambers in mice which will tolerate cells from other mammals (these are known as SCID mice). Success in novel method would be the precursor for the production of new human tissues to repair specific defects.