Authors:
Sharma AK, Bury MI, Marks AJ, Fuller NJ, Meisner JW, Tapaskar N, Halliday LC, Matoka DJ, & Cheng EY
Summary:
Animal models that have been utilized 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 utilized 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 non-human primate bladder (baboon) augmentation model. Cell sorted CD105(+)/CD73(+)/CD34(-)/CD45(-) baboon MSCs transduced with 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, Hematoxylin and Eosin (H&E), and immunofluorescent staining 10 weeks post augmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed >90% of the cells were GFP(+)/muscle marker(+) and >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&E staining revealed a lack of infiltration of inflammatory cells in grafted animals, and in corresponding kidneys, and ureters. Simple cystometry indicated recovery between 28-40% of native bladder capacity. Data demonstrate MSC/SIS composites support regeneration of bladder tissue and validate this new bladder augmentation model.
Source:
Stem Cells; (11/23/10)