Bioengineered bladder patches constructed from multilayered adipose-derived stem cell sheets for bladder regeneration.
Bioengineered bladder patches constructed from multilayered adipose-derived stem cell sheets for bladder regeneration.
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DOI：
10.1016/j.actbio.2018.12.016
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发表时间：
2019-02
影响因子：
9.7
通讯作者：
Ying Wang;Shukui Zhou;Ranxing Yang;Qingsong Zou;Kaile Zhang;Qinghua Tian;Weixin Zhao;Lijuan Zong;Q. Fu
中科院分区：
文献类型：
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作者：
Ying Wang;Shukui Zhou;Ranxing Yang;Qingsong Zou;Kaile Zhang;Qinghua Tian;Weixin Zhao;Lijuan Zong;Q. Fu
细胞种子支架是细胞移植用于膀胱修复和重建的一种常见途径。然而，当收获细胞悬浮液时，蛋白水解酶通常会导致细胞外基质损伤和细胞间连接丢失。为了克服这个问题，我们开发了一种由多孔支架和多层脂肪源性干细胞（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膀胱再生的可行性。脂肪来源的干细胞（ASCs）用超小超顺磁性氧化铁（USPIO）纳米颗粒标记。采用多层uspio标记的ASC片和多孔聚乙醇酸支架构建ASC贴片。为监测生物工程膀胱贴片在活体动物中的分布和定位，分别于移植后2 周、4 周和8 周进行磁共振成像（MRI）检查。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。扫描电镜显示，细胞片与支架紧密粘附。MRI显示uspio标记的ASC片移植部位的低信号持续8 周。免疫荧光显示，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贴片恢复膀胱功能，增强膀胱容量。uspio标记的ASC贴片为图像引导组织工程提供了一个有希望的前景，并且作为一种安全有效的膀胱再生治疗策略具有很大的前景。脂肪源性干细胞（ASC）薄片避免了酶解作用，保留了细胞间相互作用和细胞外基质（ECM）蛋白，这在组织再生中表现出巨大的潜力。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膀胱再生的可行性。组织工程膀胱贴片修复膀胱功能，促进尿路上皮、平滑肌、神经细胞和血管的再生。此外，超小型超顺磁性氧化铁（USPIO）标记的膀胱贴片可以通过无创MRI在体内长时间动态监测。因此，uspio标记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。
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 SignificanceAdipose-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.