Laboratoire d'Organogénèse Expérimentale de l'Université Laval, Génie tissulaire et régénération: LOEX, Centre de recherche FRSQ du Centre hospitalier affilié universitaire de Québec and Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
J Pediatr Urol. 2011 Jun;7(3):276-82. doi: 10.1016/j.jpurol.2011.03.002. Epub 2011 Apr 27.
Bladder reconstruction performed by enterocystoplasty or with bioengineered substitutes is still associated with complications, which led us to develop an autologous vesical equivalent (VE). This model has already proven its structural conformity. The challenge is to reconstruct our model in a more physiological environment, with the use of a bioreactor that mimics the dynamic of bladder filling and emptying, to acquire physiological properties.
Fibroblasts and urothelial cells evolved in a three-dimensional culture to obtain a reconstructed VE. This was then cultured in our bioreactor which delivers a cyclic pressure increase up to 15 cm H(2)O, followed by a rapid decrease, to achieve a dynamically cultured VE (dcVE). To compare with the statically cultured VE, the dcVE was characterized using histology and immunofluorescence. The mechanical resistance was evaluated by uniaxial tensile tests, and the permeability level was measured with 14C-urea.
Compared to our static model, the dynamic culture led to a urothelium profile like that of native bladder. Permeability analysis displayed a profile comparable to native bladder, coinciding with basal cell organization in the dcVE, while an appropriate resistance for suturing and handling was shown.
This new alternative method offers a promising avenue for regenerative medicine. It is distinguished by its autologous character and its efficiency as a barrier to urea. These properties could significantly reduce inflammation, necrosis, and therefore, possible rejection.
通过肠膀胱成形术或使用生物工程替代品进行膀胱重建仍然会伴有并发症,这促使我们开发了一种自体膀胱等效物(VE)。该模型已经证明了其结构一致性。挑战在于在更生理的环境中重建我们的模型,使用生物反应器来模拟膀胱充盈和排空的动态,以获得生理特性。
纤维母细胞和尿路上皮细胞在三维培养中进化,以获得重建的 VE。然后将其在我们的生物反应器中培养,该生物反应器可施加循环压力增加至 15 厘米 H2O,然后迅速降低压力,以实现动态培养的 VE(dcVE)。为了与静态培养的 VE 进行比较,使用组织学和免疫荧光对 dcVE 进行了表征。通过单轴拉伸试验评估机械阻力,并用 14C-尿素测量渗透性水平。
与我们的静态模型相比,动态培养导致尿路上皮轮廓类似于天然膀胱。渗透分析显示出与天然膀胱相似的轮廓,与 dcVE 中的基底细胞组织相对应,同时显示出适当的缝合和处理阻力。
这种新的替代方法为再生医学提供了一个有前途的途径。它的特点是自体特性和作为尿素屏障的效率。这些特性可以显著减少炎症、坏死,从而减少可能的排斥反应。