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Animal models that have been used to examine the regenerative capacity of cell‐seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell‐sorted CD105 + /CD73 + /CD34 − /CD45 −  baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%–50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&amp;E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti‐GFP antibody revealed that &gt;90% of the cells were GFP + /muscle marker +  and &gt;70% were GFP + /Ki‐67 +  demonstrating grafted cells were present and actively proliferating within the grafted region. Trichrome staining of MSC/SIS‐augmented bladders exhibited typical bladder architecture and quantitative morphometry analyses revealed an approximate 32% and 52% muscle to collagen ratio in unseeded versus seeded animals, respectively. H&amp;E staining revealed a lack of infiltration of inflammatory cells in grafted animals and in corresponding kidneys and ureters. Simple cystometry indicated recovery between 28% and 40% of native bladder capacity. Data demonstrate MSC/SIS composites support regeneration of bladder tissue and validate this new bladder augmentation model. S TEM  C ELLS  2011;29:241–250

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