University of California, San Francisco, CA, USA.
Silicon Kidney LLC, San Ramon, CA, USA.
Nat Commun. 2023 Aug 29;14(1):4890. doi: 10.1038/s41467-023-39888-2.
The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.
终末期肾病的确定性治疗方法是肾移植,但肾源有限,且存在移植后并发症。而可植入的生物人工肾可以同时解决这两个问题,同时提高患者的生活质量和延长其寿命。可植入的生物人工肾需要一个包含肾细胞的生物反应器,以复制关键的天然细胞功能,如水分和溶质的重吸收以及代谢和内分泌功能。在这里,我们报告了一种概念验证性的可植入生物反应器,其中包含硅纳米孔膜,为人类肾上皮细胞提供一定程度的免疫保护。在没有全身抗凝或免疫抑制治疗的情况下,将其植入猪体内 7 天后,我们发现细胞的存活率和功能保持在>90%,其转运蛋白基因表达和维生素 D 激活正常或升高。尽管植入了异种移植物模型,但我们发现细胞损伤很小,且受体细胞因子水平没有提示发生超急性排斥反应。这些初步数据证实了利用硅纳米孔膜的可植入生物反应器进行肾细胞治疗的潜在可行性。