Improved contractile potential in detrusor microtissues from pediatric patients with end stage lower urinary tract dysfunction

Abstract

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.

Neurogenic Lower Urinary Tract Dysfunction in Spinal Dysraphism: Morphological and Molecular Evidence in Children

“…Our study also highlighted the role of autophagy (a recycling process that degrades cellular components and provides energy) as a factor influencing the remodeling of SMCs, and the alteration of functionality in bladder smooth muscle tissue in NLUTD [ 77 ]. Furthermore, in a recent study, we demonstrated that SMCs from pediatric hostile bladders lose their characteristic disease phenotype in a three-dimensional (3D) microtissue culture and recover an improved contractile phenotype similar to that of healthy control subjects [ 78 ]. Overall, the actual mechanisms underlying the functional and structural changes in bladder SMCs in health and disease are not well understood.…”