Regeneration of the ureter using a scaffold-free live-cell structure created with the bio-three-dimensional printing technique
Regeneration of the ureter using a scaffold-free live-cell structure created with the bio-three-dimensional printing technique
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DOI：
10.1016/j.actbio.2022.10.006
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发表时间：
2023-06-13
影响因子：
9.7
通讯作者：
Nagayasu，Takeshi
中科院分区：
文献类型：
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作者：
Takagi，Katsunori;Matsumoto，Keitaro;Nagayasu，Takeshi
输尿管狭窄可由输尿管损伤、放射治疗、输尿管结石、尿路感染和输尿管子宫内膜异位症引起，通常需要输尿管重建。尽管组织工程、自体替代组织移植和应用各种皮瓣的外科技术已经用于输尿管再生，都取得了一些成功，但每种方法都有其优点和缺点。作为替代方案，我们仅使用活细胞创建了第一个人工输尿管结构，并将其移植到健康的大鼠输尿管中。使用正常人真皮成纤维细胞和人脐静脉内皮细胞产生球体，随后使用生物三维打印机层压。将层压球体成型为管状结构后，将人工输尿管移植到活体大鼠体内。2-12周后处死动物，观察大体和病理学特征。在0-1级肾积水大鼠的人工输尿管腔内，观察到输尿管上皮再生，其厚度在实验过程中增加。还观察到肌层的再生，随着时间的推移从正常输尿管侧向人工输尿管结构延伸。然而，在12周结束时未观察到完全再生。尽管所有病例均观察到输尿管扩张，但其强度低于预期。因此，我们使用仅细胞的结构实现了短段输尿管再生。这一发现表明，通过应用替代策略，这种方法，如改变细胞类型和组成，再生在整个长度的输尿管可能是可能的在future.Statement的重要性到目前为止，输尿管再生技术已占主导地位的高分子量化合物和自体组织的使用，并没有报道再生使用的结构完全由细胞。这是第一个报告输尿管再生使用管状结构的堆叠球体。虽然这项研究只实现了短段输尿管再生，但将来可以通过应用其他策略（如改变细胞类型）实现输尿管长度更长比例的再生。该研究为实现未来完全再生的目标提供了基础。
Ureteral strictures, which can be caused by ureteral injury, radiation therapy, ureterolithiasis, urinary tract infections, and ureteral endometriosis, typically require ureteral reconstruction. Although tissue engineering, autologous alternative tissue transplantation, and surgical techniques applying various flaps have been carried out for ureteral regeneration, all with some success, each method has its advantages and disadvantages. As an alternative, we created the first artificial ureter structures using only live cells and grafted them into healthy rat ureters. Spheroids were created using normal human dermal fibroblasts and human umbilical vein endothelial cells and subsequently laminated using a bio-three-dimensional printer. After molding the laminated spheroids into tubular structures, the artificial ureters were transplanted into live rats. After 2–12 weeks, the animals were sacrificed and their gross and pathological features were examined. In the artificial ureteral lumen of rats with Grade 0-1 hydronephrosis, regeneration of the ureteral epithelium was observed, the thickness of which increased over the course of the experiment. Regeneration of the muscular layer was also observed, extending from the normal ureteral side toward the artificial ureter structure over time. However, complete regeneration was not observed at the end of 12 weeks. Although ureteral peristalsis was noted in all cases, it was weaker than expected. Therefore, we achieved short-segment ureteral regeneration using a cell-only structure. This finding suggests that by applying alternative strategies to this method, such as changing the cell type and composition, regeneration over the entire length of the ureter may be possible in the future.Statement of significanceUntil now, ureteral regeneration techniques have been dominated by the use of high-molecular-weight compounds and autologous tissues, and there have been no reports of regeneration using structures made entirely of cells. This is the first report of ureteral regeneration using a tubular structure made from stacked spheroids. Although this study only attained short-segment ureteral regeneration, regeneration of the ureter over a much longer proportion of its length can be achieved in the future by applying other strategies, such as changing the cell type. This study provides a foundation to achieve the future goal of complete regeneration.