Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
Volume 108, Issue 7, Pages 3045-3055Publisher
WILEY
DOI: 10.1002/jbm.b.34633
Keywords
collagen; detrusor muscle; stem cells; tissue engineering; urinary bladder
Funding
- Fromm Fellowship, Children's Research Center, Childrens University Hospital Zurich
- Helmut Horten Foundation, University Zurich, Switzerland
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Objective The gold standard for bladder regeneration in end-stage bladder disease is the use of intestinal tissue, which is however associated with significant long-term complications. Our study aims to bioengineer functional detrusor muscle combining bladder smooth muscle cells (SMC) and SMC-like adipose-derived stem cells (pADSC) in compressed collagen (CC) hydrogels and to investigate biocompatibility and tissue regeneration of such detrusor-equivalents in a rat detrusorectomy model. Methods Compressed collagen hydrogels seeded with 1 x 10(6) or 4 x 10(6) SMC alone or in combination with pADSC in a 1:1 ratio were investigated. Morphology, phenotype, and viability as well as proteomic secretome analysis were assessed in the 1:1 co-cultures and the respective monocultures. The hydrogels were implanted into rat bladders after partial detrusorectomy. Bladders were harvested 8 weeks after transplantation, and assessed for tissue morphology, detrusor regeneration, neo-vascularization and -innervation. Results Co-cultured cells exhibited native SMC morphology, high viability and proliferated to form microtissues in vitro. The pro-angiogenic factors angiogenin, vascular endothelial growth factor (VEGF)-A and -D were increased in the secretome of the pADSC samples. After 8 weeks of in vivo, the regenerated bladder wall showed a multilayered structure containing all bladder wall components. The overall performance of the bladder wall regeneration of CC seeded with 4 x 10(6)cells was significantly better than with 1 x 10(6) cells and the combination SMC:pADCS performed slightly better than SMC alone. Conclusion Compressed collagen possesses an adequate regenerative potential to promote regeneration of bladder wall tissue in vivo. Seeded with a combination of pADSC and SMC this may well be the first step towards a functional bladder reconstruction especially in patients suffering of end-stage bladder diseases.
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