Control of Organogenesis: Towards Effective Tissue Engineering
The word “Organogenesis” is defined as “the production and development of the organs of an animal or plant” [1]. In the context of medical research, it has traditionally been applied to the natural processes of fetal development but it is now beginning to
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M. Unbekandt, J. Davies
Contents 6.1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 61
6.2
Features of Natural Organogenesis . . . . . . . 61
6.3
Engineered Organogenesis . . . . . . . . . . . . . . 63
6.3.1
Extracorporeal Tissue Engineering . . . . . . . 63
6.3.2
Intracorporeal Tissue Engineering . . . . . . . . 64
6.4
A Longer-Term Vision for Tissue Engineering: Synthetic Morphology . . . . . . 66 References . . . . . . . . . . . . . . . . . . . . . . . . . . 67
6.1
Introduction The word “Organogenesis” is defined as “the production and development of the organs of an animal or plant” [1]. In the context of medical research, it has traditionally been applied to the natural processes of fetal development but it is now beginning to be applied also to the creation of living organs, or organ substitutes, by artificial means. It is this latter meaning that is most relevant to this book and most of this chapter will therefore focus on artificial organogenesis. It will be helpful, though, to review the basic features of natural organogenesis first, because the most successful methods of artificial organogenesis tend to build on them.
6.2
Features of Natural Organogenesis Each organ of the human body forms in its own way but decades of research, mainly in mice, have revealed some constant themes. One is that most organs develop relatively autonomously; rudiments of lungs, salivary glands, kidneys, prostates, etc., can be removed from embryos and placed, in isolation, in organ culture where they will grow organotypically in relatively simple media with no influence from other embryonic tissues [2]. In the context of a real embryo there is, of course, some communication between different organs of the body, which is responsible for keeping their development in step, amongst other things, but the ability of the organs to develop to a large extent in culture demonstrates the extent to which the information required for controlling organogenesis resides within an organ itself. This point is critical to the whole enterprise of tissue engineering. Fully-formed organs contain many cell types and have complicated anatomies. Visceral organs, with which this review is mainly concerned, typically contain epithelial tubes, which may or may not be branched, smooth muscles, vascular endothelia cells, neurons, and stroma. Each of these broad categories may include several different cell types. For example, epithelial tubes may contain simple cells involved simply with building “plumbing” and also specialized cells that undertake various types of excretion or solute exchange. Their rudiments, though, are usually simple and consist of very few
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tissue types. The metanephric (“permanent”) kidney, for example, consists initially of two tissues, an epithelial tubule called the ureteric bud and a surrounding mesenchyme. The epithelial tubule apparently consists of two cell types (“tip” and “stalk”) and the mesenchyme may consist of just a single cell type. Over the course o
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