Towards a bioengineered kidney: recellularization strategies for decellularized native kidney scaffolds

Patients with end-stage renal disease often undergo dialysis as a partial substitute for kidney function while waiting for their only treatment option: a kidney transplant. Several research directions emerged for alternatives in support of the ever-growing numbers of patients. Recent years brought big steps forward in the field, with researchers questioning and improving the current dialysis devices as well as moving towards the design of a bioengineered kidney. Whole-organ engineering is also being explored as a possibility, making use of animal or human kidney scaffolds for engineering a transplantable organ. While this is not a new strategy, having been applied so far for thin tissues, it is a novel approach for complex organs such as the kidneys. Kidneys can be decellularized and the remaining scaffold consisting of an extracellular matrix can be repopulated with (autologous) cells, aiming at growing ex vivo a fully transplantable organ. In a broader view, such organs might also be used for a better understanding of fundamental biological concepts and disease mechanisms, drug screening and toxicological investigations, opening new pathways in the treatment of kidney disease.

Decellularization of whole organs has been widely explored and described; therefore, this manuscript only briefly reviews some important considerations with an emphasis on scaffold decontamination, but focuses further on recellularization strategies. Critical aspects, including cell types and sources that can be used for recellularization, seeding strategies and possible applications beyond renal replacement are discussed.