Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, 200233 Shanghai, China.
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China.
Acta Biomater. 2019 Feb;85:131-141. doi: 10.1016/j.actbio.2018.12.016. Epub 2018 Dec 12.
Cell-seeded scaffolds are a common route of cell transplantation for bladder repair and reconstruction. However, when cell suspensions are harvested, proteolytic enzymes often cause extracellular matrix damage and loss of intercellular junctions. To overcome this problem, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered adipose-derived stem cell (ASC) sheets, and evaluated its feasibility for bladder regeneration in a rat model. Adipose-derived stem cells (ASCs) were labeled with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles. ASC patches were constructed using multilayered USPIO-labeled ASC sheets and porous polyglycolic acid scaffolds. To monitor the distribution and localization of bioengineered bladder patches in live animals, magnetic resonance imaging (MRI) was performed 2 weeks, 4 weeks and 8 weeks after transplantation. The bladder regenerative potential of ASC patches was further evaluated by urodynamic and histological analysis. Scanning electron microscopy indicated that cell sheets adhered tightly to the scaffold. MRI showed hypointense signals that lasted up to 8 weeks at the site of USPIO-labeled ASC sheet transplants. Immunofluorescence demonstrated that these tissue-engineered bladder patches promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Urodynamic testing revealed that the ASC patch restored bladder function with augmented capacity. The USPIO-labeled ASC patch provides a promising perspective on image-guided tissue engineering and holds great promise as a safe and effective therapeutic strategy for bladder regeneration. STATEMENT OF SIGNIFICANCE: Adipose-derived stem cell (ASC) sheets avoid enzymatic dissociation and preserve the cell-to-cell interactions and extracellular matrix (ECM) proteins, which exhibit great potential for tissue regeneration. In this study, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered ASC sheets, and evaluated its feasibility for bladder regeneration in a rat model. Tissue-engineered bladder patches restored bladder function and promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Moreover, ultrasmall super-paramagnetic iron oxide (USPIO)-labeled bladder patches can be dynamically monitored in vivo by noninvasive MRI for long periods of time. Therefore, The USPIO-labeled bladder patch provides a promising image-guided therapeutic strategy for bladder regeneration.
细胞种植支架是膀胱修复和重建中细胞移植的常用途径。然而，当收获细胞悬液时，蛋白酶通常会导致细胞外基质损伤和细胞间连接丢失。为了解决这个问题，我们开发了一种由多孔支架和多层脂肪来源干细胞（ASC）片组成的生物工程三维膀胱贴片，并在大鼠模型中评估了其用于膀胱再生的可行性。脂肪来源干细胞（ASCs）用超小超顺磁性氧化铁（USPIO）纳米颗粒标记。ASC 贴片是使用多层标记有 USPIO 的 ASC 片和多孔聚乙二醇酸支架构建的。为了在活体动物中监测生物工程膀胱贴片的分布和定位，在移植后 2 周、4 周和 8 周进行磁共振成像（MRI）。通过尿动力学和组织学分析进一步评估 ASC 贴片的膀胱再生潜力。扫描电子显微镜表明细胞片紧密附着在支架上。MRI 显示，在 USPIO 标记的 ASC 片移植部位，低信号持续长达 8 周。免疫荧光染色表明，这些组织工程膀胱贴片促进了尿路上皮、平滑肌、神经细胞和血管的再生。尿动力学测试显示，ASC 贴片恢复了膀胱功能，增加了容量。USPIO 标记的 ASC 贴片为图像引导组织工程提供了有前景的视角，作为一种安全有效的膀胱再生治疗策略具有很大的潜力。
脂肪来源干细胞（ASC）片避免了酶解，保留了细胞间相互作用和细胞外基质（ECM）蛋白，这对组织再生具有巨大潜力。在这项研究中，我们开发了一种由多孔支架和多层 ASC 片组成的生物工程三维膀胱贴片，并在大鼠模型中评估了其用于膀胱再生的可行性。组织工程膀胱贴片恢复了膀胱功能，促进了尿路上皮、平滑肌、神经细胞和血管的再生。此外，超小超顺磁性氧化铁（USPIO）标记的膀胱贴片可以通过非侵入性 MRI 进行长时间动态监测。因此，USPIO 标记的膀胱贴片为膀胱再生提供了一种有前途的图像引导治疗策略。
