Kidney regeneration: Where we are and future perspectives

Abstract

In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an efficient bioengineered kidney, these cells must be attached to the organ and then maturated into the bioractors, which simulates the human body environment. A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the field of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengineered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.

Keywords: Decellularization; Extra cellular matrix; Kidney regeneration; Regenerative medicine; Stem cells.

Figure 1

Vascular and collecting system casting of a kidney. Red: Arteries; Blue: Veins; Yellow: Ureter and collecting system. Permission of Wake Forest Institute for Regenerative Medicine.

Figure 2

Regeneration of a tissue/organ.

Figure 3

A decellularized pig kidney scaffold and its extra cellular matrix after decellularization. A: Decellularized pig kidney scaffold; B: Hematoxylin and eosin staining of the decellularized pig kidney scaffold shows a decellularized extracellular matrix (× 200); C: Hematoxylin and eosin staining of the decellularized pig kidney scaffold shows a decellularized extracellular matrix (× 400). Permission of Wake Forest Institute for Regenerative Medicine.

Figure 4

Normal kidney glomerulous visualized through scanning electron microscopy ( magnification × 250). Permission of Wake Forest Institute for Regenerative Medicine.