Changing concepts of bladder regeneration

Abstract

During the last decade, there has been a dramatic increase in studies aimed at regeneration of the urinary bladder. Many studies employed animal-derived or synthetic materials as grafts for experimental bladder augmentation models, with or without additional measures to promote regeneration, such as autologous cell transplantation or growth factor loading. However, in spite of encouraging results in several reports, few methodologies have shown proven definitive clinical utility. One major problem in these studies is the lack of a clear distinction between native and regenerated bladder in total bladder function after augmentation. Another crucial problem is the absorption and shrinkage of larger grafts, which may result from insufficient vascular supply and smooth muscle regeneration. In contrast, researchers have recently attempted to establish alternative regenerative strategies for treating bladder diseases, and have employed far more diverse approaches according to the various pathological conditions to be treated. For total replacement of the bladder after cystectomy for invasive bladder cancer, urothelium-covered neobladder with non-urinary tract backbone remains a viable choice. In addition, functional bladder diseases such as urinary incontinence, weak detrusor, or non-compliant fibrotic bladder have also been major targets for many leading research groups in this field. These conditions are studied much more from different therapeutic standpoints, aiming at the prevention or reversal of pathological conditions in muscle remodeling or neural control. Such altered research direction would inevitably lead to less surgically based basic biological research, and also would include a far wider spectrum of adult and pediatric bladder diseases, from overactive bladder to dysfunctional voiding.

Porcine extracellular matrix scaffolds in reconstructive urology: An ex vivo comparative study of their biomechanical properties

“…This has previously been attributed to substantial graft shrinkage precipitated by long-term exposure to urine after in vivo implantation (Kanematsu et al, 2007). However, our results demonstrate that more immediate complications such as significant decreases in TBC and C may arise due to fundamental differences in biomechanical properties between native bladder tissue and ECM scaffolds.…”

Coadministration of Platelet-Derived Growth Factor-BB and Vascular Endothelial Growth Factor with Bladder Acellular Matrix Enhances Smooth Muscle Regeneration and Vascularization for Bladder Augmentation in a Rabbit Model

“…For bladder reconstruction, the crucial requirements are smooth muscle regeneration and vascularization. 24 Urination is accomplished through bladder smooth muscle tissue contraction. Therefore, smooth muscle regeneration is essential for the recovery of contractile function of tissue-engineered neobladder.…”

“…Vascularization is to establish a prompt and complete vascular network to supply nutrient and oxygen, which facilitate cell survival and bladder wall regeneration. 10,24 We found that angiogenic growth factors, such as basic fibroblast growth factor (bFGF), VEGF, and nerve growth factor (NGF), had been investigated in cell-free tissue-engineering approaches to facilitate bladder regeneration in a rat model. 13,15,19 In these researches, angiogenesis and recovery of bladder function were improved by the exogenous bioactive factors.…”

“…The smooth muscle regeneration and angiogenesis are extremely crucial in tissue engineering of bladder, since many studies showed that smooth muscle regeneration and vascularization were unsatisfied when the reconstructed area was relative large. 10,24 Therefore, we used a bioactive factor cocktail (two growth factors, PDGF-BB and VEGF) and investigated their role in II(B)] in the experimental rabbit neobladder were higher than those in the control group at 1 and 3 months after surgery (*p < 0.05). At 6 months postoperation, PCC and RPC in the two groups were similar and were also similar with those in the native bladder tissue.…”

Regeneration of Native-Like Neo-Urinary Tissue from Nonbladder Cell Sources

“…There is clearly a compelling medical need for an improved approach to eliminate, or substantially reduce, the complications potentially associated with the current standard of care. 1,2 Tissue engineering principles have been successfully applied to provide implantable cell-seeded matrices for use in the reconstruction, repair, augmentation, or replacement of laminarly organized luminal organs and tissue structures, such as a bladder or a bladder component, typically composed of urothelial and smooth muscle cell (SMC) layers. [3][4][5][6][7] SMCs may be derived from the patient's own tissue, including the bladder, urethra, ureter, and other urogenital tissue.…”