Urinary bladder smooth muscle engineered from adipose stem cells and a three dimensional synthetic composite

Abstract

Human adipose stem cells were cultured in smooth muscle inductive media and seeded into synthetic bladder composites to tissue engineer bladder smooth muscle. 85:15 poly-lactic-glycolic acid bladder dome composites were cast using an electropulled microfiber luminal surface combined with an outer porous sponge. Cell seeded bladders expressed smooth muscle actin, myosin heavy chain, calponinin, and caldesmon via RT-PCR and immunoflourescence. Nude rats (n=45) underwent removal of half their bladder and repair using: (i) augmentation with the adipose stem cell seeded composites, (ii) augmentation with a matched acellular composite, or (iii) suture closure. Animals were followed for 12 weeks post-implantation and bladders were explanted serially. Results showed that bladder capacity and compliance were maintained in the cell seeded group throughout the 12 weeks, but deteriorated in the acellular scaffold group sequentially with time. Control animals repaired with sutures regained their baseline bladder capacities by week 12, demonstrating a long term limitation of this model. Histological analysis of explanted materials demonstrated viable adipose stem cells and increasing smooth muscle mass in the cell seeded scaffolds with time. Tissue bath stimulation demonstrated smooth muscle contraction of the seeded implants but not the acellular implants after 12 weeks in vivo. Our study demonstrates the feasibility and short term physical properties of bladder tissue engineered from adipose stem cells.

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

“…It was also noted that native baboon urothelium had invaded the grafted area to provide a watertight barrier, and seeded bMSCs were not present as determined by antibody staining. This phenomenon has been reported in other species as well [9,12].…”

“…Although a majority of the bladder augmentation studies have been performed in canine, rodent, or rabbit models, [10][11][12][13] there exists the conundrum as to whether these models are good representations of the lower urinary tract in humans as anatomical and physiological differences often result in poorly translatable data. The high regenerative capacity of urothelial cells in various models may possibly confound overall analyses of regenerative process in cystectomized animals.…”

“…Studies describing this phenomenon in nude rats demonstrate the rapid invasion of native urothelium onto the luminal side of cystectomized bladders that have been seeded with cells. This rapid invasion of urothelium may prevent the luminally seeded cell populations from proliferating and contributing to the grafts [9,12]. Alternatively, the cells on the luminally seeded side of the graft may undergo cell death as a consequence of being in contact with urine.…”

179 Human umbilical mesenchymal stem cells-seeded bladder acellular matrix grafts for reconstruction of bladder defects in a canine model

“…Recently, a variety of synthetic and organic matrices used to reconstruct damaged bladders in animal models have been reported [31,[35][36][37][38]. In the present study, we selected BAMG as a biomaterial to reconstruct the bladder.…”

Aspects of Urological Tissue Engineering

“…(Murtuza, 2009) Adipose derived mesenchymal stem cells have also been utilized in bladder regenerative settings and provide a means to obtain a multipotent cell source through adipose tissue aspirates. (Jack, 2009) Adipose derived mesenchymal stem cells maintain an approximate 3% of all nucleated cells within a sample of aspirate. Jack et al seeded adipose derived mesenchymal stem cells upon PLGA scaffolds and implanted them in 50% cystectomized athymic nude rats.…”