Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland.
Department of Embryology and Histology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-092, Bydgoszcz, Poland.
Stem Cell Res Ther. 2018 Nov 28;9(1):328. doi: 10.1186/s13287-018-1070-3.
The tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model.
ADSCs isolated from a superficial abdominal Camper's fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation.
Sixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells.
The data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.
由于临床需要为需要膀胱替代的患者提供新的治疗方案，因此，膀胱组织工程学迅速发展。大多数膀胱扩大研究都是在小型啮齿动物或兔模型中进行的。由于在大型动物模型中，对组织工程移植物在膀胱扩大中再生能力的研究数量不足，因此无法将这项技术成功转化为临床应用。本研究旨在评估脂肪来源干细胞（ADSCs）在大型动物模型中治疗性膀胱壁缺损再生中的作用。
从腹部 Camper 筋膜的浅层分离 ADSC，用 PKH-26 示踪染料标记，然后将其接种到膀胱去细胞基质（BAM）移植物中。猪接受半胱切除术，然后仅用 BAM（n=10）或用自体 ADSC 接种的 BAM（n=10）进行膀胱扩大成形术。在扩大成形术后 3 个月，对重建的膀胱进行宏观、组织学、免疫荧光、分子和影像学评估。
16 只动物（每组 n=8）在 3 个月的随访中存活，没有严重并发症。组织工程膀胱功能正常，膀胱和上尿路均无排尿后残余尿液的迹象。ADSC 增强了组织工程膀胱的再生，但在中央移植物区域的再生过程并不完全。只有一小部分植入的 ADSC 存活并分化为平滑肌和内皮细胞。
数据表明，ADSC 支持膀胱壁大缺损的再生，但在中央移植物区域的再生过程并不完全。干细胞通过旁分泌作用间接增强膀胱再生。
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