Relevance of ureteric bud development and branching to tissue engineering, regeneration and repair in acute and chronic kidney disease

Abstract

Chronic kidney disease is expected to continue to be a major health problem. There remains a huge shortage of donor tissues. A potential solution is to engineer a kidney-like tissue capable of performing differentiated renal functions. These functions are strikingly dependent upon appropriate three-dimensional relationships established during development, including those arising from branching morphogenesis of the ureteric bud. The ureteric bud, an 'iterative tip-stalk generator' (ITSG) forming the scaffold around which the kidney is built, can be cultured and propagated ex vivo while retaining the capacity to induce and appropriately interact with nascent nephrons. Progress has been made toward construction of a ureteric bud from cells. The myriad functions of the kidney are critically dependent upon its three-dimensional spatial architecture established by branching of the ureteric bud. Ureteric bud branching morphogenesis can be recapitulated ex vivo; we discuss how this intrinsic property of the ureteric bud might be exploited for engineering of kidney-like tissues potentially useful for the treatment of chronic kidney disease, acute kidney injury, and/or other renal diseases.