1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
2 The Diabetes Research Institute Federation, Miami, FL, USA.
Cell Transplant. 2017 Nov;26(11):1780-1791. doi: 10.1177/0963689717722787.
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 cm graft. In the first and second groups, urinary bladders were reconstructed with small intestinal submucosa (SIS) seeded with 10 × 10 or 4 × 10 ADSCs/cm, respectively. In the third and fourth groups, urinary bladders were augmented with SIS seeded with 10 × 10 or 4 × 10 BM-MSCs/cm, 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 × 10/cm) compared to lower density (4 × 10/cm). 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.
目前,人们正在探索各种利用不同细胞和生物材料的组织工程技术来从头构建新的膀胱壁,但到目前为止,还没有一种方法明显优于其他方法。本研究旨在确定来源于不同组织(骨髓[BM-MSCs]和脂肪组织[ADSCs])的间充质干细胞(MSCs)在构建组织工程化膀胱中的平滑肌再生潜力方面是否存在差异,并确定用于膀胱平滑肌再生的最佳 MSC 数量。48 只大鼠接受半胱切除术和膀胱扩大术,用约 0.8cm 的移植物进行膀胱扩大术。在第一组和第二组中,用小肠黏膜下层(SIS)分别接种 10×10 或 4×10 ADSCs/cm 的细胞来构建膀胱;在第三组和第四组中,用 SIS 分别接种 10×10 或 4×10 BM-MSCs/cm 的细胞来构建膀胱;在第五组中,用 SIS 而不接种细胞来构建膀胱。第六组(对照组)则保持完整。通过实时聚合酶链反应(RT-PCR)和组织学检查来评估平滑肌再生。组织学上,用 ADSC 接种的移植物构建的膀胱与用 BM-MSCs 接种的移植物构建的膀胱之间没有显著差异,但与用 MSC 接种的移植物(10×10/cm)构建的膀胱相比,用 MSC 接种的移植物(4×10/cm)构建的膀胱中平滑肌形成明显增加。分子分析显示,用 ADSC 接种的移植物构建的膀胱表达更高水平的平滑肌肌球蛋白重链、钙调蛋白和纽蛋白。未接种 SIS 的膀胱纤维化且缺乏平滑肌。ADSCs 和 BM-MSCs 具有相当的平滑肌再生潜力,但用于移植物制备的 MSC 数量显著影响组织工程化膀胱中的平滑肌含量。