Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.
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使用硅纳米孔膜进行植入生物反应器对肾细胞疗法的可行性。

DOI:
10.1038/s41467-023-39888-2
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发表时间:
2023-08-29
影响因子:
16.6
通讯作者:
Roy, Shuvo
Roy, Shuvo
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim, Eun Jung;Chen, Caressa;Gologorsky, Rebecca;Santandreu, Ana;Torres, Alonso;Wright, Nathan;Goodin, Mark S.;Moyer, Jarrett;Chui, Benjamin W.;Blaha, Charles;Brakeman, Paul;Vartanian, Shant;Tang, Qizhi;Humes, H. David;Fissell, William H.;Roy, Shuvo

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终末期肾病的最终治疗方法是肾移植,但仍受到器官可用性和移植后并发症的限制。或者,植入式生物人工肾可以解决这两个问题,同时提高病人的生活质量和寿命。可植入的生物人工肾需要含有肾细胞的生物反应器来复制关键的天然细胞功能,例如水和溶质重吸收,以及代谢和内分泌功能。在这里,我们报告了一种概念验证的植入式生物反应器,含有硅纳米孔膜,为人类肾上皮细胞提供一定水平的免疫保护。在没有全身抗凝或免疫抑制治疗的情况下植入猪体内7天后,我们表明细胞保持>90%的活力和功能,具有正常或升高的转运蛋白基因表达和维生素D活化。尽管植入异种移植模型,我们发现细胞表现出最小的损伤,受体细胞因子水平并不提示超急性排斥反应。这些初始数据证实了利用硅纳米孔膜进行肾细胞治疗的可植入生物反应器的潜在可行性。一种具有含细胞生物反应器的可植入生物人工肾可用于治疗终末期肾病。在本文中,作者通过在异种移植模型中植入后维持人细胞活力和功能来证明植入式生物反应器的可行性。
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. An implantable bioartificial kidney with a cell-containing bioreactor could be used to treat end-stage renal disease. Here the authors demonstrate the feasibility of an implantable bioreactor by maintaining human cell viability and functionality after implantation in a xenograft model.
轨道剪切应力调节原发性肾小管上皮细胞的分化和屏障功能。
DOI: 10.1097/mat.0000000000000723
发表时间: 2018
期刊: ASAIO journal (American Society for Artificial Internal Organs : 1992)
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