Bioengineering Kidneys for Transplantation

Abstract

One in ten Americans suffer from chronic kidney disease, and close to 90,000 people die each year from causes related to kidney failure. Patients with end-stage renal disease are faced with two options: hemodialysis or transplantation. Unfortunately, the reach of transplantation is limited because of the shortage of donor organs and the need for immunosuppression. Bioengineered kidney grafts theoretically present a novel solution to both problems. Herein we discuss the history of bioengineering organs, the current status of bioengineered kidneys, considerations for the future of the field, and challenges to clinical translation. We hope that by integrating principles of tissue engineering, and stem cell and developmental biology, bioengineered kidney grafts will advance the field of regenerative medicine while meeting a critical clinical need.

A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

“…Human renal proximal tubule cells are immunologically active, which when adapted with non-biodegradable fibres, allows membranes to act as scaffolds for the cells and as an immunoprotective barrier which previous filtration methods lacked. Phase I/II clinical trials demonstrated that the RAD was able to filter urine at a rudimentary level, improve metabolism, reduce pro-inflammatory cytokines, and improve cardiovascular stability [40], whilst improving long-term survival [41].…”

“…To recapitulate complex kidney function, epithelial, endothelial, and mesangial cells in sufficient numbers are required [41]. However, application of cell type is dependent upon the renal disease in question, therefore making it difficult to choose between tubular cells or glomerular epithelial cells, and research failed to identify whether it would be better to introduce progenitor cells for integration into existing structures or support cells which encourage existing renal parenchyma to proliferate and repair.…”

“…The minimum criteria for any kidney scaffold are that it is biocompatible, able to mimic the basic organ structure (including vasculature), be able to withstand forces caused by fluid flow whilst having filtration properties, is safe to use, and durable enough to be surgically handled whilst maintaining in vitro and in vivo integrity. Perfusion, filtration, secretion, absorption, and drainage of urine whilst maintaining homeostasis and control of hemodynamic, immunologic, and endocrine functions are also important factors [41]. Other obstacles include the lack of high-resolution cell deposition [139], controlled cell distribution, vascularization [110], and innervation.…”

“…Kidney decellularization success is often reliant upon the organ harvest, which must have occurred prior to proteolysis (4-6 h post-mortem) [41], and the age of the kidney has also been shown to have an effect on cellular repopulation [187]. Xeno matrices, including the use of porcine tissues, have also been investigated to reduce some of these barriers [183,188,189], since the organ size is comparable to humans [190][191][192][193] and porcine matrices are able to promote the adhesion, survival, and maintenance of human cells [180,[194][195][196].…”

Short term ex vivo storage of kidneys cause progressive nuclear ploidy changes of renal tubular epitheliocytes

“…There have been several paradigm shifting discoveries related to organ transplantation 1 2 3 4 5 6 7 . Chief among them includes the innovations that pertain to organ storage ex vivo 8 9 10 11 12 .…”