Renal bioengineering with scaffolds generated from human kidneys.

Abstract

Background: In 2012, about 16,487 people received kidney transplants in the USA whereas 95,022 candidates were on the waiting list at the end of the year. Moreover, more than 2,600 kidneys procured annually for transplantation are discarded for a variety of reasons. We hypothesize that this pool of discarded kidneys could in part meet the growing, urgent need for transplantable kidneys using current methods for organ bioengineering and regeneration and surgical transplantation. The recellularization of extracellular matrix (ECM) scaffolds has the potential to meet the uniquely ambitious engineering challenges posed by complex solid organs such as the kidney.

Summary: Attempts to manufacture and implant simpler, hollow structures such as bladders, vessels, urethras, and segments of the upper airways have been successful in the short and mid terms. However, the bioengineering of complex solid organs such as the kidney is a more challenging task that requires a different approach. In previous studies, we showed that decellularized porcine kidneys yield renal ECM scaffolds that preserve their basic architecture and structural components, support cell growth in vivo and in vitro, and maintain a patent vasculature capable of sustaining physiological blood pressure. In a subsequent report, using the same methods, we found that detergent-based decellularization of discarded human renal kidneys preserved their innate ECM framework, biochemical properties, and angiogenic capacity and - importantly - a patent vascular network. Furthermore, the process resulted in the clearance of immunogenic antigens, which has monumental implications for clinical outcomes in the long term in terms of graft rejection. Consequently, these kidneys show promise in bioengineering and transplantation. We refer to this avenue of research and development as 'cell-scaffold technology'.

Key messages: In 2011, more than 4,700 patients died while on the waiting list for a kidney transplant. In this context, we believe that cell-scaffold technology has the potential to form a bridge between regenerative medicine and transplantation surgery. These methods, in theory, could provide a potentially inexhaustible source of transplantable organs. Unfortunately, current investigations are still in their very early stages and clinical translation is not immediately available in the short term. Thus, identifying the most important obstacles confronting cell-scaffold technology and focusing research efforts in this direction will be important for advancing the state of the art and meeting the clinical needs. We believe that cell-scaffold technology research and development would benefit greatly from a deeper understanding of the physiological mechanisms underlying the natural organogenesis, regeneration, and repair that characterize embryonic humans and simpler organisms. Furthermore, the importance of vascularization - the fundamental caveat of modern surgery - cannot be overstated, especially when discussing the implantation of de novo organs.