Challenges in a larger bladder replacement with cell‐seeded and unseeded small intestinal submucosa grafts in a subtotal cystectomy model

Abstract

OBJECTIVE To evaluate small intestinal submucosa (SIS), unseeded or seeded, as a possible augmentation material in a canine model of subtotal cystectomy. MATERIALS AND METHODS In all, 22 male dogs had a 90% partial cystectomy and were then divided into three groups. At 1 month after the initial cystectomy, dogs in group 1 (unseeded, six) and group 2 (seeded, six) received a bladder augmentation with a corresponding SIS graft. The dogs in group 3 (ten) received no further surgery and were considered the surgical control group. All dogs were evaluated before and after surgery with blood chemistry, urine culture, intravenous urography, cystograms and cystometrograms. After surgery (at 1, 5 and 9 months), the bladders were examined using routine histology and immunohistochemistry. RESULTS All 22 dogs survived the subtotal cystectomy, and 18 survived their intended survival period. One dog, in group 2 (seeded), was killed at 1 month after augmentation due to bladder perforation caused by a large piece of incompletely absorbed SIS. Three other dogs (group 1, two; and group 2, one) were killed within 2 months after augmentation due to bladder obstruction by stones. Group 1 and group 2 SIS grafts had moderate to heavy adhesion, graft shrinkage, and some had bone and calcification at the graft site. Histologically, there was limited bladder regeneration in both groups. Interestingly, dogs in group 3 at 1 month after cystectomy (when group 1 and 2 received their augmentations) had severely shrunken bladders and histologically had severe inflammation, fibroblast infiltration and muscle hypertrophy. These results verify the subtotal cystectomy model. CONCLUSIONS The use of seeded or unseeded SIS in a subtotal cystectomy model does not induce the same quality and quantity of bladder regeneration that is seen in the 40% non‐inflammatory cystectomy model. This study provides important insights into the process of regeneration in a severely damaged bladder. The results led us to re‐evaluate the critical elements required for a complete bladder replacement using tissue‐engineering techniques.

Experimental bladder regeneration using a poly-L-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells

“…32 One of the possible strategies to increase the biocompatibility of the graft and reduce complications could be based on the seeding of the implant with cells. 33 To date, several cell sources have been suggested including pluripotent stem cells, human umbilical mesenchymal stem cells, urothelial, and smooth muscle cells. [34][35][36][37] In our studies for enhancing the integrative properties of grafts, we applied allogenic BMSCs which have immunosuppressive action [17][18][19] and are able to differentiate in different directions.…”

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

“…The limited graft size in rodent models provides an inadequate model of regeneration due to the rate at which the regenerative process occurs. Small augmented areas tend to regenerate within a matter of weeks, whereas larger grafts, as seen in canine models, can take up to several months to regenerate completely [9,14,15]. More importantly, there exist anatomical differences between the lower nonhuman primates (NHPs) species and humans that include the musculature component of the lower urinary tract further questioning the translational validity of lower NHP models [16][17][18].…”

Expression of VEGF and collagen using a latex biomembrane as bladder replacement in rabbits

“…For the appropriate development of native tissue, the biodegradable molds must be practically impermeable to urine on their luminal surface and should permit cellular and vascular growth in the portion in contact with native tissue, an essential factor for cell survival (17). The neovascularization of regenerated tissues is of great importance since tissues do not grow more than a few millimeters unless they are vascularized (13).…”