title: A nonhuman primate model for urinary bladder regeneration using autologous sources of bone marrow-derived mesenchymal stem cells.
abstract: 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&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >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% and 40% of native bladder capacity. Data demonstrate MSC/SIS composites support regeneration of bladder tissue and validate this new bladder augmentation model.
authors: Division of Pediatric Urology; Children's Memorial Hospital of Chicago, Chicago, Illinois, USA. arun-sharma@northwestern.edu
authors: Arun K
authors: AK
authors: Sharma
authors: Matthew I
authors: MI
authors: Bury
authors: Andrew J
authors: AJ
authors: Marks
authors: Natalie J
authors: NJ
authors: Fuller
authors: Jay W
authors: JW
authors: Meisner
authors: Natalie
authors: N
authors: Tapaskar
authors: Lisa C
authors: LC
authors: Halliday
authors: Derek J
authors: DJ
authors: Matoka
authors: Earl Y
authors: EY
authors: Cheng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D015653:Cystectomy; D005109:Extracellular Matrix / Q000502:physiology; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics; D007413:Intestinal Mucosa; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009852:Omentum / Q000502:physiology*; D010215:Papio; D012038:Regeneration / Q000502:physiology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D001743:Urinary Bladder / Q000502:physiology* / Q000601:surgery
chemical_list: D049452:Green Fluorescent Proteins