Moreno-Manzano Victoria, Mellado-López Maravillas, Morera-Esteve Maria Jose, Alastrue-Agudo Ana, Bisbal-Velasco Viviana, Forteza-Vila Jerónimo, Serrano-Aroca Ángel, Vera-Donoso César David
Neuronal and Tissue Regeneration Lab, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Facultad de Veterinaria y Ciencias Experimentales, Universidad Católica de Valencia San Vicente Mártir, c/Guillem de Castro 94, Valencia 46001, Spain.
Regen Biomater. 2020 Mar;7(2):161-169. doi: 10.1093/rb/rbz049. Epub 2019 Dec 22.
Decellularized natural bladder matrices (neobladders) represent an exciting means to regenerate the bladder following bladder cancer-associated cystectomy. In this study, we compare the evolution of decellularized matrices with recellularized matrices by seeding it with human adipose-derived mesenchymal stem cells (ADSC) after implantation following partial cystectomy in rats. We discovered significant anatomical differences since 10 days after neobladder implantation with the ADSC-containing matrices promoting a significant recovery of mature p63- and cytokeratin 7-positive urothelium. We also discovered significantly induced expression of the vimentin mesoderm marker in the submucosal layer in ADSC-seeded matrices. Interestingly, we found a higher expression of smooth muscle actin in transversal and longitudinal smooth muscle layers with ADSC-seeded matrices. Furthermore, ADSC also showed increased vascularization and nerve innervation of the neobladder as determined by the distribution of CD31 and S100β reactivity, respectively. We believe that ADSC and their paracrine-acting pro-regenerative secretome within decellularized matrices represent an efficient bladder substitution strategy; however, we require a fuller understanding of the mechanisms involved before clinical studies can begin.
去细胞化天然膀胱基质（新膀胱）是一种令人兴奋的方法，可用于在膀胱癌相关膀胱切除术后再生膀胱。在本研究中，我们在大鼠部分膀胱切除术后植入去细胞化基质后，通过接种人脂肪来源间充质干细胞（ADSC），比较去细胞化基质与再细胞化基质的演变。我们发现，自新膀胱植入10天后，含ADSC的基质出现显著的解剖学差异，促进了成熟的p63和细胞角蛋白7阳性尿路上皮的显著恢复。我们还发现，在接种ADSC的基质中，黏膜下层波形蛋白中胚层标记物的表达显著诱导。有趣的是，我们发现接种ADSC的基质在横向和纵向平滑肌层中平滑肌肌动蛋白的表达更高。此外，分别通过CD31和S100β反应性的分布确定，ADSC还显示新膀胱的血管生成和神经支配增加。我们认为，ADSC及其在去细胞化基质中的旁分泌促再生分泌组代表了一种有效的膀胱替代策略；然而，在开始临床研究之前，我们需要更全面地了解其中涉及的机制。
