Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina.
Biomed Res Int. 2022 Jul 13;2022:9018074. doi: 10.1155/2022/9018074. eCollection 2022.
The excessive demand for organ transplants has promoted the development of strategies that increase the supply of immune compatible organs, such as xenotransplantation of genetically modified pig organs and the generation of bioartificial organs. We describe a method for the partial replacement of rat endothelial cells for human endothelial cells in a rat's kidney, obtaining as a final result a rat-human bioartificial kidney. First, in order to maintain parenchymal epithelial cells and selectively eliminate rat endothelial cells, three methods were evaluated in which different solutions were perfused through the renal artery: 0.1% sodium dodecyl sulfate (SDS), 0.01% SDS, and hyperosmolar solutions of sucrose. Then, partially decellularized kidneys were recellularized with human endothelial cells and finally transplanted in an anesthetized rat. The solution of 0.1% SDS achieved the highest vascular decellularization but with high degree of damage in the parenchyma side. On the contrary, 0.01% SDS and hyperosmolar solutions achieved a partial degree of endothelial decellularization. TUNEL assays reveal that hyperosmolar solutions maintained a better epithelial cell viability contrasting with 0.01% SDS. Partially decellularized kidneys were then recellularized with human endothelial cells. Histological analysis showed endothelial cells attached in almost all the vascular bed. Recellularized kidney was transplanted in an anesthetized rat. After surgery, recellularized kidney achieved complete perfusion, and urine was produced for at least 90 min posttransplant. Histological analysis showed endothelial cells attached in almost all the vascular bed. Therefore, endothelial decellularization of grafts and recellularization with human endothelial cells derived from transplant recipients can be a feasible method with the aim to reduce the damage of the grafts.
对器官移植的过度需求促使人们开发了增加免疫相容性器官供应的策略，例如基因修饰猪器官的异种移植和生物人工器官的产生。我们描述了一种在大鼠肾脏中部分替代人内皮细胞为大鼠内皮细胞的方法，最终得到大鼠-人生物人工肾脏。首先，为了维持实质上皮细胞并选择性地消除大鼠内皮细胞，我们评估了通过肾动脉灌注三种不同溶液的方法：0.1%十二烷基硫酸钠（SDS）、0.01% SDS 和高渗蔗糖溶液。然后，用人内皮细胞对部分去细胞化的肾脏进行再细胞化，最后在麻醉大鼠中进行移植。0.1% SDS 溶液实现了最高的血管去细胞化，但实质侧损伤程度较高。相反，0.01% SDS 和高渗溶液实现了部分内皮细胞去细胞化。TUNEL 检测显示，高渗溶液保持了更好的上皮细胞活力，与 0.01% SDS 形成对比。然后，用人内皮细胞对部分去细胞化的肾脏进行再细胞化。组织学分析显示内皮细胞几乎附着在所有的血管床中。将再细胞化的肾脏移植到麻醉大鼠中。手术后，再细胞化的肾脏实现了完全灌注，移植后至少 90 分钟产生尿液。组织学分析显示内皮细胞几乎附着在所有的血管床中。因此，移植物的内皮细胞去细胞化和用来自移植受者的人内皮细胞再细胞化可能是一种可行的方法，旨在减少移植物的损伤。
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