Bioengineered transplants: stem cell reversal of chronic kidney disease

Chronic kidney disease (CKD) is an indolent yet unrelenting condition that affects 10% of the global population. CKD often progresses to end-stage renal disease (ESRD), and resulted in 1.2 million deaths in 2017. The prevalence of CKD continues to rise, with increasingly stark health and economic consequences. Current treatment seeks to delay the onset of ESRD, with kidney transplantation representing the only potentially curative option. However, donor organ supplies are unpredictable, and as demand continues to increase, waiting list times are increasingly untenable for late-stage patients. Transplantation is also associated with complications, immunosuppression, and unending expense. Therefore, alternatives or adjuncts are desperately needed. One particularly attractive option is the rejuvenation of a patient’s own failing organs via whole tissue bioengineering. Utilising the techniques of decellularisation, wherein a surgically excised organ is stripped of its dysfunctional cells into an extracellular matrix scaffold ex vivo, and recellularisation, where the organ is repopulated with the patient’s own in vitro-derived stem cells prior to re-implantation, whole tissue bioengineering may improve patient outcomes. However, it remains an iterative practice that has yet to achieve translational relevance. This is primarily due to the problems associated with applying animal-derived research findings to human clinical practice. In general, scaling established protocols from animal to human kidneys remains challenging and elusive. Due to the compartmentalised structure of the kidneys, methods of establishing viable cellular growth remain to be refined to the extent necessary for clinical trials. This review will explore the remaining challenges facing whole-organ tissue bioengineering in the context of CKD.