Regenerative pharmacology of the bladder

Regenerative pharmacology can be defined as “the application of pharmacological sciences to accelerate, optimize and characterize (either in vitro or in vivo) the development, maturation and function of bioengineered and regenerating tissues” (Andersson & Christ, 2007). Generally, two approaches may be used: (a) the “active” (i.e., directing) approach, exemplified by the use of growth factors and different pharmacological agents or bioactive molecules to alter cell proliferation, differentiation, and function in a desired fashion, and (b) the “passive” (i.e., dissecting) approach, as illustrated through the use of established pharmacological methods to evaluate and compare salient characteristics of endogenously regenerated or bioengineered cells and tissues (e.g., how closely do the requisite signal transduction mechanisms of an engineered or regenerating tissue or organ compare with the native tissue or organ?). Both of these approaches are currently used in regenerative medicine, and the goal of this chapter as well as Chapter 3 is to illustrate these basic principles in detail using organ regeneration as observed in the bladder. Why the bladder? Somewhat surprisingly perhaps, the bladder has actually been at the leading edge of clinical translation in tissue engineering and regenerative medicine. This is partly attributable to the rather extensive intrinsic regenerative capacity of this organ (Table 2-1). Regenerative pharmacology has been used as a tool to understand not only the phenomenon of endogenous bladder regeneration (with and without the use of scaffolds or cells) but also to optimize bioengineered bladder constructs for implantation (see Chapter 3 for more details). Because of the bladder's natural regenerative capacity, regenerative pharmacology not only can be used to characterize “normal” bladder regeneration (e.g., functionally, structurally, molecularly) but can also be used to identify mechanisms to improve regeneration in scenarios in which it is compromised.