Abstract
To evaluate the mesenchymal stem cells (MSCs) influence on cytokines and matrix metalloproteinases (MMPs) expression in rat bladder wall regeneration. MSCs cultures from the bone marrow were established. Acellular matrices from the bladder submucosa were prepared. Bladders were reconstructed using cell-seeded (n = 5) and unseeded (n = 5) grafts. MSCs were injected into the bladder wall (n = 5), bladders were incised and MSCs were injected into the circulation (n = 5) or were left intact (n = 5). Animals were killed after 3 months. Bladder histology and immunohistochemical staining of IL-2, IL-4, IL-6, IL-10, TNF-α, TGF-β1, IFN-γ, MMP-2, and MMP-9 were done. Bladders reconstructed with cell-seeded grafts mimicked native tissue, while unseeded grafts revealed shrinkage and morphological irregularities. There were no morphological changes in bladders of other groups. Different pattern of cytokine and MMP expression was observed. Increased expression of anti-inflammatory cytokines and MMPs in bladder promotes detrusor regeneration.
Highlights
The gold standard for bladder creation after radical cystectomy is the use of gastrointestinal segments
It has been demonstrated that these smart matrices promote urinary tract regeneration, it should be strongly emphasized that a non-physiological concentration or improper selection of growth factors can lead to tissue overgrowth, fibrosis, or other complications (Kanematsu et al 2003; Loai et al 2010; Nuininga et al 2010)
Understanding that molecular aspects of bladder regeneration are fundamental for future research in this field, we investigated the efficacy of bone marrow mesenchymal stem cells (MSCs) in improving the bladder muscle regeneration and analyzed the cytokines and matrix metalloproteinases (MMPs) expression in this process
Summary
The gold standard for bladder creation after radical cystectomy is the use of gastrointestinal segments. Using bowel as a substitute is associated with complications (Nieuwenhuijzen et al 2008). This encouraged research in tissue engineering for bladder reconstruction. The key idea of this approach is construction of the new bladder wall from autologous cells expanded in vitro and seeded on biodegradable scaffold followed by transplantation for the completion of the regeneration process (Atala et al 2006; Drewa et al 2009; Sharma et al 2011). There are many diseases in which autologous urothelial cells and myocytes cannot be harvested for in vitro bladder wall construction including bladder cancer, which is the most common indication for cystectomy, forms of neuropathic bladder, idiopathic detrusor overactivity, interstitial cystitis or other forms of chronic cystitis
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