Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.
Eun Jung KimCaressa ChenRebecca GologorskyAna SantandreuAlonso TorresNathan WrightMark S GoodinJarrett MoyerBenjamin W ChuiCharles BlahaPaul BrakemanShant VartanianQizhi TangH David HumesWilliam H FissellShuvo RoyPublished in: Nature communications (2023)
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.
Keyphrases
- cell therapy
- induced apoptosis
- gene expression
- wastewater treatment
- cell cycle arrest
- kidney transplantation
- end stage renal disease
- mesenchymal stem cells
- stem cells
- chronic kidney disease
- single molecule
- peritoneal dialysis
- endoplasmic reticulum stress
- mental health
- endothelial cells
- atrial fibrillation
- dna methylation
- signaling pathway
- cell death
- venous thromboembolism
- electronic health record
- risk assessment
- risk factors