Spinal dysraphism, most commonly myelomeningocele, is the typical cause of a neurogenic lower urinary tract dysfunction (NLUTD) in childhood. The structural changes in the bladder wall in spinal dysraphism already occur in the fetal period and affect all bladder wall compartments. The progressive decrease in smooth muscle and the gradual increase in fibrosis in the detrusor, the impairment of the barrier function of the urothelium, and the global decrease in nerve density, lead to severe functional impairment characterized by reduced compliance and increased elastic modulus. Children present a particular challenge, as their diseases and capabilities evolve with age. An increased understanding of the signaling pathways involved in lower urinary tract development and function could also fill an important knowledge gap at the interface between basic science and clinical implications, leading to new opportunities for prenatal screening, diagnosis, and therapy. In this review, we aim to summarize the evidence on structural, functional, and molecular changes in the NLUTD bladder in children with spinal dysraphism and discuss possible strategies for improved management and for the development of new therapeutic approaches for affected children.

Autologous cell-based tissue engineering has been proposed as a treatment option for end stage lower urinary tract dysfunction (ESLUTD). However, it is generally accepted that cells isolated from patient bladders retain the pathological properties of their tissue of origin and therefore need to be improved before they can serve as a cell source for tissue engineering applications. We hypothesize that human three-dimensional (3D) microtissues of detrusor smooth muscle cells (SMCs) are valuable ex vivo disease models and potent building blocks for bladder tissue engineering. Detrusor SMCs isolated from bladder wall biopsies of pediatric ESLUTD patients and healthy controls were expanded and cultured into 3D microtissues. Gene and protein analyses were performed to explore the effect of microtissue formation on SMC viability, contractile potential, bladder wall specific extracellular matrix (ECM) composition and mediators of ECM remodeling. Through microtissue formation, remodeling and intensified cell-cell interactions, the ESLUTD SMCs lost their characteristic disease phenotype. These microtissues exhibited similar patterns of smooth muscle related contractile proteins and essential bladder wall-specific ECM components as microtissues from healthy control subjects. Thus, the presented data suggest improved contractile potential and ECM composition in detrusor SMC microtissues from pediatric ESLUTD patients. These findings are of great relevance, as 3D detrusor SMC microtissues might be an appropriate cell source for autologous cell-based bladder tissue engineering.