A Nonhuman primate model for urinary bladder regeneration using autologous sources of bone marrow-derived mesenchymal stem cells

Arun K. Sharma, Matthew I. Bury, Andrew J. Marks, Natalie J. Fuller, Jay W. Meisner, Natalie Tapaskar, Lisa C. Halliday, Derek J. Matoka, Earl Y. Cheng

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)241-250
Number of pages10
JournalStem Cells
Volume29
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • Bone marrow
  • Mesenchymal stem cell
  • Nonhuman primate model
  • Smooth muscle cells
  • Tissue regeneration

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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