Does the Mesenchymal Stem Cell Source Influence Smooth Muscle Regeneration in Tissue-Engineered Urinary Bladders?

Abstract

A variety of tissue engineering techniques utilizing different cells and biomaterials are currently being explored to construct urinary bladder walls de novo, but so far no approach is clearly superior. The aim of this study was to determine whether mesenchymal stem cells (MSCs) isolated from different sources, (bone marrow [BM-MSCs] and adipose tissue [ADSCs]), differ in their potential to regenerate smooth muscles in tissue-engineered urinary bladders and to determine an optimal number of MSCs for urinary bladder smooth muscle regeneration. Forty-eight rats underwent hemicystectomy and bladder augmentation with approximately 0.8 cm2 graft. In the first and second groups, urinary bladders were reconstructed with small intestinal submucosa (SIS) seeded with 10 × 106 or 4 × 106 ADSCs/cm2, respectively. In the third and fourth groups, urinary bladders were augmented with SIS seeded with 10 × 106 or 4 × 106 BM-MSCs/cm2, respectively. In the fifth group, urinary bladders were augmented with SIS without cells. The sixth group (control) was left intact. Smooth muscle regeneration was evaluated by real-time polymerase chain reaction (RT-PCR) and histological examinations. Histologically, there were no significant differences between urinary bladders augmented with ADSCs and BM-MSCs, but there was a marked increase in smooth muscle formation in bladders augmented with grafts seeded with MSCs in higher density (10 × 106/cm2) compared to lower density (4 × 106/cm2). Molecular analysis revealed that bladders reconstructed with ADSC-seeded grafts expressed higher levels of smooth muscle myosin heavy chain, caldesmon, and vinculin. Bladders augmented with unseeded SIS were fibrotic and devoid of smooth muscles. ADSCs and BM-MSCs have comparable smooth muscle regenerative potential, but the number of MSCs used for graft preparation significantly affects the smooth muscle content in tissue-engineered urinary bladders.

Detrusor bioengineering using a cell‐enriched compressed collagen hydrogel

“…Looking closer at the different bladder wall components in the regenerated tissue, we unexpectedly found that SMC bundle formation was more pronounced in the samples seeded with 1 × 10 6 cells and the control. This is in contrast with the findings of Pokrywczynska who showed that a higher density of MSCs significantly improved the smooth muscle content in tissue-engineered urinary bladders after 3 months (Pokrywczynska et al, 2017). A possible explanation could be the earlier time point in our study.…”

“…We and other authors have demonstrated, that unseeded grafts do not allow for proper urinary bladder regeneration (Pokrywczynska et al, 2017). However, these papers were mainly using SIS (Chung et al, 2005;Pokrywczynska et al, 2017) or synthetic materials (Horst et al, 2017;Jack et al, 2009) and all used a cystoplasty model with full thickness replacement of the bladder wall. This might explain the different findings.…”

Understanding the role of mesenchymal stem cells in urinary bladder regeneration—a preclinical study on a porcine model

“…In our previous study, we found that source of mesenchymal stem cells (bone morrow vs adipose tissue) had no impact on regeneration of tissue-engineered urinary bladder. However, regeneration outcome is strictly dependent on the number of cells used for the reconstruction [ 12 ].…”

The different expression of key markers on urothelial holoclonal, meroclonal, and paraclonal cells in in vitro culture

“…Therefore urothelial cells could not only prevent an urine leakage to the deeper graft layers by biomaterial sealing but also protect smooth muscle cells or mesenchymal stem cells seeded on the outer graft surface from cytotoxic effect of urine (Pokrywczynska et al, 2017(Pokrywczynska et al, , 2018b. It was indicated that urothelial cells are more resistant to urine compared to smooth muscle cells or mesenchymal stem cells.…”

“…It was indicated that urothelial cells are more resistant to urine compared to smooth muscle cells or mesenchymal stem cells. Therefore urothelial cells could not only prevent an urine leakage to the deeper graft layers by biomaterial sealing but also protect smooth muscle cells or mesenchymal stem cells seeded on the outer graft surface from cytotoxic effect of urine (Pokrywczynska et al, 2017(Pokrywczynska et al, , 2018b.…”