Open AccessA Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow‐Derived Mesenchymal Stem Cells
Author(s) -
Sharma Arun K.,
Bury Matthew I.,
Marks Andrew J.,
Fuller Natalie J.,
Meisner Jay W.,
Tapaskar Natalie,
Halliday Lisa C.,
Matoka Derek J.,
Cheng Earl Y.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.568
Subject(s) - biology , mesenchymal stem cell , baboon , pathology , urinary bladder , regeneration (biology) , cd34 , masson's trichrome stain , stem cell , staining , cystectomy , bladder augmentation , anatomy , microbiology and biotechnology , bladder cancer , urinary system , urology , endocrinology , medicine , genetics , cancer
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. S TEM C ELLS 2011;29:241–250